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片岡宏介

徳島大学

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2024年11月14日更新

職名: 教授
電話: 088-633-7384
電子メール: kataoka-k@tokushima-u.ac.jp
学歴: 1993/3: 大阪大学歯学部卒業
学位: 博士(歯学) (大阪大学) (2000年2月)
職歴・経歴: 1996/7: 大阪大学歯学部助教
2001/11: 米国アラバマ大学バーミンガム校ワクチンセンターポスドク
2008/1: 大阪大学歯学部附属病院講師
2008/3: 徳島大学准教授，ヘルスバイオサイエンス研究部予防歯学分野
2013/4: 昭和大学歯学部兼任講師
2016/3: 大阪歯科大学歯学部口腔衛生学講座准教授
2016/4: 朝日大学歯学部非常勤講師
2023/4: 広島大学歯学部客員教授
2023/4: 鹿児島大学非常勤講師

専門分野・研究分野: 予防歯科学 (Preventive Dentistry)
口腔衛生学 (Oral Health)
粘膜免疫

研究者総覧で最新データを確認する

2024年11月14日更新

専門分野・研究分野: 予防歯科学 (Preventive Dentistry)
口腔衛生学 (Oral Health)
粘膜免疫
担当経験のある授業科目: (基礎系)国家試験・CBT対策講義 (学部)
ソーシャルワークの基盤と専門職 (学部)
ソーシャルワークの基盤と専門職(専門) (学部)
ソーシャルワークの理論と方法 (学部)
ソーシャルワークの理論と方法(専門) (学部)
ソーシャルワーク実習 (学部)
ソーシャルワーク実習指導 (学部)
ソーシャルワーク演習 (学部)
ソーシャルワーク演習(専門) (学部)
予防歯学 (大学院)
予防歯学演習 (大学院)
予防歯科学実習 (学部)
予防歯科学B 講義 (学部)
予防歯科学各論 (学部)
予防歯科学実習 (学部)
予防歯科学総論 (学部)
保健医療と福祉 (学部)
児童・家庭福祉 (学部)
刑事司法と福祉 (学部)
卒業研究 (学部)
卒業研究(4年生) (学部)
口腔と健康 (共通教育)
口腔保健増進学概論 (大学院)
口腔保健学特論 (大学院)
口腔保健学臨床系課題実習 (大学院)
口腔保健学課題研究演習 (大学院)
口腔保健栄養福祉学特論 (大学院)
口腔保健福祉学特別演習 (大学院)
口腔保健福祉学特別研究 (大学院)
口腔健康管理学特論 (大学院)
口腔感染症学 (大学院)
国際口腔保健学 (大学院)
地域福祉と包括的支援体制 (学部)
基礎看護学 (学部)
実践口腔科学実習 (大学院)
小児口腔保健学 (大学院)
心理学と心理的支援 (学部)
権利擁護を支える法制度 (学部)
歯科衛生士概論 (学部)
研究基礎ゼミ (学部)
社会と歯科医療 (学部)
社会保障 (学部)
社会学と社会システム (学部)
社会福祉概論 (学部)
社会福祉調査の基礎 (学部)
福祉サービスの組織と経営 (学部)
統合臨床講義 (学部)
総合医科学 (学部)
総合歯科学二 (学部)
総合歯科学五 (学部)
衛生公衆衛生学 (学部)
貧困に対する支援 (学部)
障害者福祉 (学部)
顎口腔発育・社会歯科学実験実習 (大学院)
高齢者・障害者口腔機能管理学 (大学院)
高齢者福祉 (学部)
指導経験: 1人 (修士), 1人 (博士)

研究者総覧で最新データを確認する

2024年11月14日更新

専門分野・研究分野: 予防歯科学 (Preventive Dentistry)
口腔衛生学 (Oral Health)
粘膜免疫

研究テーマ: 新規粘膜ワクチンアジュバントの開発, 口腔内細菌定着機構メカニズムの解明とその応用 (経鼻ワクチン, 樹状細胞, 唾液分泌型IgA, 歯周病原性菌, 定着阻害)
(新規粘膜アジュバントの開発と機能解明)

著書

片岡宏介 :
チェアサイドQ&A マスク生活が続きますが，口腔の健康にどんな影響がありますか?,
2023年5月. 片岡宏介 :
歯科衛生士テキスト口腔衛生学-口腔保健統計を含む- 第4版,
2022年3月. 片岡宏介 :
粘膜免疫学,
医歯薬出版株式会社, 東京, 2021年12月. 片岡宏介 :
歯科衛生士テキスト口腔衛生学,
2020年3月. 片岡宏介, 雫石聰, 藤橋浩太郎 :
「コレラトキシンの粘膜投与によるIgA産生B細胞の誘導」,
科学評論社, 東京, 2007年6月.

(キーワード): mucosa / B-1a B cell / IL-5 / LPS
(文献検索サイトへのリンク): ● CiNii @ 国立情報学研究所 (CRID): 1522543655786684416

(CiNii: 1522543655786684416)

論文

Kosuke Kataoka, Kusumoto Yutaka, Ueda Mizuki, Moriya Taiki and Tomura Michio :
Sublingual immune cell clusters and dendritic cell distribution in the oral cavity,
JCI Insight, e167373, 2024.

(キーワード): Denrdritic cells / Sublingual immune cells / cluster / T cells

吉松英樹, 片岡宏介, 三宅達郎 :
天然由来成分ヒノキチオールが Streptococcus mutans の増殖およびバイオフィルム形成に与える影響,
口腔衛生学会雑誌, Vol.74, No.1, 52-58, 2024年.

(キーワード): ヒノキチオール / バイオフィルム / Streptococcus mutans
(徳島大学機関リポジトリ): ● Metadata: 119329
(出版サイトへのリンク): ● Publication site (DOI): 10.5834/jdh.74.1_52
(文献検索サイトへのリンク): ● CiNii @ 国立情報学研究所 (CRID): 1390580626907854592; ● Search Scopus @ Elsevier (DOI): 10.5834/jdh.74.1_52

(徳島大学機関リポジトリ: 119329, DOI: 10.5834/jdh.74.1_52, CiNii: 1390580626907854592) Qianying Li, Kosuke Kataoka, Hideki Yoshimatsu and Tatsuro Miyake :
Effects of D-psicose on growth and hyphal development of Candida albicans.,
ECronicon Microbiology, Vol.19, No.9, 1-10, 2023. Koyanagi Kayo, Kosuke Kataoka, Fujihashi Kohtaro and Miyake Tatsuro :
Human salivary protein-derived peptides specific-salivary SIgA antibodies enhanced by nasal double DNA adjuvant in mice play an essential role in preventing Porphyromonas gingivalis colonization: an in-vitro study,
BMC Oral Health, Vol.23, 2023.

(要約): We previously showed that fimbriae-bore from Poryphyromonas gingivalis (Pg), one of the putative periodontopathogenic bacteria specifically bound to a peptide domain (stat23, prp21) shared on statherin or acidic proline-rich protein 1 (PRP1) molecule of human salivary proteins (HSPs). Here, we investigated whether the nasal administration of DNA plasmid expressing Flt3 ligand (pFL) and CpG oligodeoxynucleotide 1826 as double DNA adjuvant (dDA) with stat23 and prpr21 induces antigen (Ag)-specific salivary secretory IgA (SIgA) antibodies (Abs) in mice. Further, we examined that stat23- and prpr21-specific salivary SIgA Abs induced by dDA have an impact on Pg-binding to human whole saliva-coated hydroxyapatite beads (wsHAPs). C57BL/6N mice were nasally immunized with dDA plus sta23 or/and prp21 peptide as Ag four times at weekly intervals. Saliva was collected one week after the final immunization and was subjected to Ag-specific ELISA. To examine the functional applicability of Ag-specific SIgA Abs, SIgA-enriched saliva samples were subjected to Pg binding inhibition assay to wsHAPs. Significantly elevated levels of salivary SIgA Ab to stat23 or prp21 were seen in mice given nasal stat23 or prp21 with dDA compared to those in mice given Ag alone. Of interest, mice nasally given the mixture of stat23 and prp21 as double Ags plus dDA, resulted in both stat23- and prp21-specific salivary SIgA Ab responses, which are mediated through significantly increased numbers of CD11c dendritic cell populations and markedly elevated Th1 and Th2 cytokines production by CD4 T cells in the mucosal inductive and effector tissues. The SIgA Ab-enriched saliva showed significantly reduced numbers of live Pg cells binding to wsHAPs as compared with those in mice given double Ags without dDA or naïve mice. Additionally, saliva from IgA-deficient mice given nasal double Ags plus dDA indicated no decrease of live Pg binding to wsHAPs. These findings show that HSP-derived peptides-specific salivary SIgA Abs induced by nasal administration of stat23 and prp21 peptides plus dDA, play an essential role in preventing Pg attachment and colonization on the surface of teeth, suggesting a potency that the SIgA may interrupt and mask fimbriae-binding domains in HSPs on the teeth.
(キーワード): Humans / Mice / Animals / Porphyromonas gingivalis / Mice, Inbred C57BL / Salivary Proteins and Peptides / Immunoglobulin A / Immunoglobulin A, Secretory / Nasal Mucosa / DNA / Mice, Inbred BALB C
(徳島大学機関リポジトリ): ● Metadata: 118427
(出版サイトへのリンク): ● Publication site (DOI): 10.1186/s12903-023-02821-6
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 36829152; ● Summary page in Scopus @ Elsevier: 2-s2.0-85148934526

(徳島大学機関リポジトリ: 118427, DOI: 10.1186/s12903-023-02821-6, PubMed: 36829152, Elsevier: Scopus) 葛西礼衣, 福井誠, 柳沢志津子, 片岡宏介 :
1,450 ppmフッ化物配合歯磨剤によるブラッシング後の安静時唾液中フッ化物イオンの残存状況に関する報告,
口腔衛生学会雑誌, Vol.72, No.3, 173-177, 2022年.

(キーワード): 高濃度フッ化物配合歯磨剤 / 唾液 / フッ化物イオン濃度 / 洗口
(出版サイトへのリンク): ● Publication site (DOI): 10.5834/jdh.72.3_173
(文献検索サイトへのリンク): ● CiNii @ 国立情報学研究所 (CRID): 1390293095147335936; ● Search Scopus @ Elsevier (DOI): 10.5834/jdh.72.3_173

(DOI: 10.5834/jdh.72.3_173, CiNii: 1390293095147335936) Hideki Yoshimatsu, Kosuke Kataoka, Kohtaro Fujihashi, Tatsuro Miyake and Yoshiaki Ono :
A nasal double DNA adjuvant system induces atheroprotective IgM antibodies via dendritic cell-B-1a B cell interactions.,
Vaccine, Vol.40, No.8, 1116-1127, 2022.

(要約): We previously demonstrated that the dendritic cell (DC)-targeting nasal double DNA adjuvant system, which consists of a DNA plasmid expressing Flt3 ligand (pFL) and CpG oligodeoxynucleotide 1826 (CpG ODN), elicits specific immune responses to various antigens in the mucosal and systemic compartments. Here, we investigated, using phosphorylcholine (PC)-conjugated keyhole limpet hemocyanin (PC-KLH) as an antigen, whether the nasal double DNA adjuvant system induces protective immunity to atherosclerosis in apolipoprotein E-deficient (ApoE KO) mice. Further, we assessed the molecular and cellular mechanisms in the induction of anti-PC-specific immune responses. Nasal immunization with PC-KLH plus pFL and CpG ODN enhanced induction of PC-specific IgM in plasma, peritoneal fluids, and nasal washes when compared with mice administered PC-KLH alone. Of importance, these antibodies exhibited highly specific binding to the PC molecule, and dose-dependent binding to anti-T15 idiotype (AB1-2). Twelve weeks after the last immunization, the nasal double DNA adjuvant system with PC-KLH resulted in a reduction of atherogenesis in the aortic arch of ApoE KO mice. Therefore, we next assessed immunocytological mechanism to induce these antibodies. The nasal double DNA adjuvant system with PC-KLH resulted not only in significantly increased frequencies of CD11c DCs in the spleen, peritoneal cavity (PEC), and nasopharyngeal-associated lymphoid tissues (NALT), but also significantly increased expression of a proliferation-inducing ligand and B-cell-activating factor by CD11c DCs. In addition, the double DNA adjuvant system induced significantly increased numbers of B-1 B cells in the spleen, PEC, and NALT, and increased expression of transmembrane activator and calcium modulator and cyclophilin ligand interactor on CD5 B220 (B-1a) B cells. These findings demonstrated that the nasal double DNA adjuvant system with PC-KLH resulted in the induction of T15-like antibodies in the mucosal and systemic lymphoid tissues through interaction between DCs and B-1a B cells, and inhibited the progression of atherogenesis.
(キーワード): Adjuvants, Immunologic / Animals / Cell Communication / DNA / Dendritic Cells / Hemocyanins / Immunoglobulin M / Mice / Mice, Inbred BALB C
(徳島大学機関リポジトリ): ● Metadata: 117193
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.vaccine.2022.01.027
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 35086743; ● Search Scopus @ Elsevier (PMID): 35086743; ● Search Scopus @ Elsevier (DOI): 10.1016/j.vaccine.2022.01.027

(徳島大学機関リポジトリ: 117193, DOI: 10.1016/j.vaccine.2022.01.027, PubMed: 35086743) Kosuke Kataoka, Shigetada Kawabata, Kayo Koyanagi, Yoshiya Hashimoto, Tatsuro Miyake and Kohtaro Fujihashi :
Respiratory FimA-specific secretory IgA antibodies upregulated by DC-targeting nasal double DNA adjuvant are essential for elimination of Porphyromonas gingivalis.,
Frontiers in Immunology, Vol.12, 634923, 2021.

(要約): Our previous studies showed that a combination of a DNA plasmid encoding Flt3 ligand (pFL) and CpG oligodeoxynucleotides 1826 (CpG ODN) (FL/CpG) as a nasal adjuvant provoked antigen-specific immune responses. In this study, we investigated the efficacy of a nasal vaccine consisting of FimA as the structural subunit of () fimbriae and FL/CpG for the induction of FimA-specific antibody (Ab) responses and their protective roles against nasal and lung infection by , a keystone pathogen in the etiology of periodontal disease. C57BL/6 mice were nasally immunized with recombinant FimA (FimA) plus FL/CpG three times at weekly intervals. As a control, mice were given nasal FimA alone. Nasal washes (NWs) and bronchoalveolar lavage fluid (BALF) of mice given nasal FimA plus FL/CpG resulted in increased levels of FimA-specific secretory IgA (SIgA) and IgG Ab responses when compared with those in controls. Significantly increased numbers of CD8- or CD11b-expressing mature-type dendritic cells (DCs) were detected in the respiratory inductive and effector tissues of mice given FimA plus FL/CpG. Additionally, significantly upregulated Th1/Th2-type cytokine responses by FimA-stimulated CD4 T cells were noted in the respiratory effector tissues. When mice were challenged with live the nasal route, mice immunized nasally with FimA plus FL/CpG inhibited colonization in the nasal cavities and lungs. In contrast, controls failed to show protection. Of interest, when IgA-deficient mice given nasal FimA plus FL/CpG were challenged with nasal , the inhibition of bacterial colonization in the respiratory tracts was not seen. Taken together, these results show that nasal FL/CpG effectively enhanced DCs and provided balanced Th1- and Th2-type cytokine response-mediated FimA-specific IgA protective immunity in the respiratory tract against A nasal administration with FimA and FL/CpG could be a candidate for potent mucosal vaccines for the elimination of inhaled in periodontal patients.
(徳島大学機関リポジトリ): ● Metadata: 117501
(出版サイトへのリンク): ● Publication site (DOI): 10.3389/fimmu.2021.634923
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 33717178; ● Search Scopus @ Elsevier (PMID): 33717178; ● Search Scopus @ Elsevier (DOI): 10.3389/fimmu.2021.634923

(徳島大学機関リポジトリ: 117501, DOI: 10.3389/fimmu.2021.634923, PubMed: 33717178) Kenjiro Kobuchi, Kosuke Kataoka, Yoichiro Taguchi, Tatsuro Miyake and Makoto Umeda :
Nasal double DNA adjuvant induces salivary FimA-specific secretory IgA antibodies in young and aging mice and blocks Porphyromonas gingivalis binding to a salivary protein.,
BMC Oral Health, Vol.19, 188-196, 2019.

(要約): We previously showed that nasal administration of a combination of dendritic cell (DC) targeted DNA plasmid expressing Flt3 ligand and CpG oligodeoxynucleotides 1826 as a mucosal adjuvant (double adjuvant, DA) provoked protective immunity in the upper respiratory tract of young adult and aging mice. Here, we investigated whether the nasal DA system induces secretory (S)IgA antibodies (Abs) toward recombinant fimbrillin (rFimA) of Porphyromonas gingivalis (P. gingivalis) in the saliva of young adult and aging mice. Further, we examined the functional applicability of rFimA-specific salivary SIgA Abs. BALB/c mice (8- or 48-week-old) were nasally immunized with rFimA plus DA three times at weekly intervals. Control mice were nasally administered rFimA alone. Saliva samples were collected 1 week after the final immunization, and were subjected to rFimA-specific ELISA. To examine the functional applicability of rFimA-specific SIgA Abs, IgA-enriched saliva samples were subjected to an inhibition assay in order to assess the numbers of P. gingivalis cells bound to the salivary protein statherin. The 8- and 48-week-old mice administered nasal rFimA plus DA showed significantly increased levels of rFimA-specific SIgA Abs in saliva and elevated numbers of CD11c DCs in sublingual glands (SLGs), periglandular lymph nodes (PGLNs) and submandibular glands (SMGs) as well as nasopharyngeal-associated lymphoid tissues (NALT) compared to mice administered rFimA alone. Further, rFimA-specific SIgA Abs-containing saliva, in which IgG Abs of 8- and 48-week-old mice administered nasal rFimA plus DA were removed, significantly inhibited binding of P. gingivalis to the salivary protein. These findings show that this DA system could be an effective nasal vaccine strategy for the enhancement of P. gingivalis-specific protective immunity in the oral cavity of adolescents and older individuals.
(キーワード): Animals / DNA / Humans / Immunity / Immunoglobulin A, Secretory / Mice / Mice, Inbred BALB C / Porphyromonas gingivalis / Salivary Proteins and Peptides / Vaccines, DNA
(徳島大学機関リポジトリ): ● Metadata: 117500
(出版サイトへのリンク): ● Publication site (DOI): 10.1186/s12903-019-0886-2
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 31426773; ● Summary page in Scopus @ Elsevier: 2-s2.0-85071319191

(徳島大学機関リポジトリ: 117500, DOI: 10.1186/s12903-019-0886-2, PubMed: 31426773, Elsevier: Scopus) 片岡宏介, 国友栄治, 小渕健二朗, 上根昌子, 土居貴士, 三宅達郎 :
ヒノキチオールの唾液分泌型IgA抗体産生に与える影響,
口腔衛生学会雑誌, Vol.68, No.3, 137-144, 2018年.

(キーワード): IgA / 唾液 / ヒノキチオール
(徳島大学機関リポジトリ): ● Metadata: 117499
(出版サイトへのリンク): ● Publication site (DOI): 10.5834/jdh.68.3_137
(文献検索サイトへのリンク): ● Search Scopus @ Elsevier (DOI): 10.5834/jdh.68.3_137

(徳島大学機関リポジトリ: 117499, DOI: 10.5834/jdh.68.3_137) Yoshiko Fukuyama, D Tokuhara, Kazunori Sekine, Kosuke Kataoka, J. Davydova, M. Yamamoto, S. R. Gilbert, Y. Tokuhara, Ke. Fujihashi, J. Kunisawa, Y. Yuki, H. Kiyono, R. J. McGhee and K. Fujihashi :
Potential roles of CCR5+ CCR6+ dendritic cells induced by nasal ovalbumin plus Flt3 ligand expressing adenovirus for mucosal IgA responses.,
PLoS ONE, Vol.8, No.4, 60453, 2013.

(要約): We assessed the role of CCR5(+)/CCR6(+)/CD11b(+)/CD11c(+) dendritic cells (DCs) for induction of ovalbumin (OVA)-specific antibody (Ab) responses following mucosal immunization. Mice given nasal OVA plus an adenovirus expressing Flt3 ligand (Ad-FL) showed early expansion of CCR5(+)/CCR6(+)/CD11b(+)/CD11c(+) DCs in nasopharyngeal-associated lymphoid tissue (NALT) and cervical lymph nodes (CLNs). Subsequently, this DC subset became resident in submandibular glands (SMGs) and nasal passages (NPs) in response to high levels of CCR-ligands produced in these tissues. CD11b(+)/CD11c(+) DCs were markedly decreased in both CCR5(-/-) and CCR6(-/-) mice. Chimera mice reconstituted with bone marrow cells from CD11c-diphtheria toxin receptor (CD11c-DTR) and CCR5(-/-) or CD11c-DTR and CCR6(-/-) mice given nasal OVA plus Ad-FL had elevated plasma IgG, but reduced IgA as well as low anti-OVA secretory IgA (SIgA )Ab responses in saliva and nasal washes. These results suggest that CCR5(+)CCR6(+) DCs play an important role in the induction of Ag-specific SIgA Ab responses.
(キーワード): Adenoviridae / Administration, Intranasal / Animals / Dendritic Cells / Immunoglobulin A / Membrane Proteins / Mice / Mucous Membrane / Ovalbumin / Receptors, CCR5 / Receptors, CCR6
(出版サイトへのリンク): ● Publication site (DOI): 10.1371/journal.pone.0060453
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 23565250; ● Summary page in Scopus @ Elsevier: 2-s2.0-84875685651

(DOI: 10.1371/journal.pone.0060453, PubMed: 23565250, Elsevier: Scopus) Masaki GOTO, Agnieszka Wilk, Kosuke Kataoka, Shirish Chodankar, Nobutake Tamai, Makoto Fukui, Joachim Kohlbrecher, Hiro-O Ito and Hitoshi Matsuki :
Study on the Subgel-Phase Formation Using an Asymmetric Phospholipid Bilayer Membrane by High-Pressure Fluorometry,
Langmuir, Vol.28, No.33, 12191-12198, 2012.

(要約): The myristoylpalmitoylphosphatidylcholine (MPPC) bilayer membrane shows a complicated temperature-pressure phase diagram. The large portion of the lamellar gel (L(β)'), ripple gel (P(β)'), and pressure-induced gel (L(β)I) phases exist as metastable phases due to the extremely stable subgel (L(c)) phase. The stable L(c) phase enables us to examine the properties of the L(c) phase. The phases of the MPPC bilayers under atmospheric and high pressures were studied by small-angle neutron scattering (SANS) and fluorescence spectroscopy using a polarity-sensitive fluorescent probe Prodan. The SANS measurements clearly demonstrated the existence of the metastable L(β)I phase with the smallest lamellar repeat distance. From a second-derivative analysis of the fluorescence data, the line shape for the L(c) phase under high pressure was characterized by a broad peak with a minimum of ca. 460 nm. The line shapes and the minimum intensity wavelength (λ''(min)) values changed with pressure, indicating that the L(c) phase has highly pressure-sensible structure. The λ''(min) values of the L(c) phase spectra were split into ca. 430 and 500 nm in the L(β)I phase region, which corresponds to the formation of a interdigitated subgel L(c) (L(c)I) phase. Moreover, the phase transitions related to the L(c) phase were reversible transitions under high pressure. Taking into account the fluorescence behavior of Prodan for the L(c) phase, we concluded that the structure of the L(c) phase is highly probably a staggered structure, which can transform into the L(c)I phase easily.
(キーワード): 2-Naphthylamine / Atmospheric Pressure / Cell Membrane / Fluorometry / Gels / Lipid Bilayers / Neutron Diffraction / Phosphatidylcholines / Pressure / Scattering, Small Angle
(出版サイトへのリンク): ● Publication site (DOI): 10.1021/la3020173
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 22823885; ● Summary page in Scopus @ Elsevier: 2-s2.0-84865495527

(DOI: 10.1021/la3020173, PubMed: 22823885, Elsevier: Scopus) Etsuhisa Takahashi, Kosuke Kataoka, Irene L. Indalao, Keiko Konoha, Kazuyuki Fujii, Junji Chida, Dai Mizuno, Kohtaro Fujihashi and Hiroshi Kido :
Oral clarithromycin enhances airway IgA immunity through induction of IgA class switching recombination and B-cell activating factor of the tumor necrosis factor family molecule on mucosal dendritic cells in mice infected with influenza A virus,
Journal of Virology, Vol.86, No.20, 10924-1093, 2012.

(要約): We previously reported that the macrolide antibiotic clarithromycin (CAM) enhanced the mucosal immune response in pediatric influenza, particularly in children treated with the antiviral neuraminidase inhibitor oseltamivir (OSV) with low production of mucosal antiviral secretory IgA (S-IgA). The aims of the present study were to confirm the effects of CAM on S-IgA immune responses, by using influenza A virus (IAV) H1N1-infected mice treated with or without OSV, and to determine the molecular mechanisms responsible for the induction of mucosal IgA class switching recombination in IAV-infected CAM-treated mice. The anti-IAV S-IgA responses and expression levels of IgA class switching recombination-associated molecules were examined in bronchus-lymphoid tissues and spleens of infected mice. We also assessed neutralization activities of S-IgA against IAV. Data show that CAM enhanced anti-IAV S-IgA induction in the airway of infected mice and restored the attenuated antiviral S-IgA levels in OSV-treated mice to the levels in the vehicle-treated mice. The expression levels of B-cell-activating factor of the tumor necrosis factor family (BAFF) molecule on mucosal dendritic cells as well as those of activation-induced cytidine deaminase and Iμ-Cα transcripts on B cells were enhanced by CAM, compared with the levels without CAM treatment, but CAM had no effect on the expression of the BAFF receptor on B cells. Enhancement by CAM of neutralization activities of airway S-IgA against IAV in vitro and reinfected mice was observed. This study identifies that CAM enhances S-IgA production and neutralizing activities through the induction of IgA class switching recombination and upregulation of BAFF molecules in mucosal dendritic cells in IAV-infected mice.
(キーワード): Administration, Oral / Animals / Antibodies, Neutralizing / Antiviral Agents / B-Cell Activating Factor / Bronchi / Clarithromycin / Cytidine Deaminase / Dendritic Cells / 女性 (female) / Immunity, Mucosal / Immunoglobulin A / Immunoglobulin Class Switching / Influenza A Virus, H1N1 Subtype / Mice / Mice, Inbred BALB C / Orthomyxoviridae Infections / Oseltamivir / Spleen / Tumor Necrosis Factor-alpha
(出版サイトへのリンク): ● Publication site (DOI): 10.1128/JVI.01207-12
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 22896605; ● Summary page in Scopus @ Elsevier: 2-s2.0-84869061538

(DOI: 10.1128/JVI.01207-12, PubMed: 22896605, Elsevier: Scopus) Yoshiko Fukuyama, D. Tokuhara, Kosuke Kataoka, S. R. Gilbert, R. J. McGhee, Y. Yuki, H. Kiyono and K Fujihashi :
Novel vaccine development strategies for inducing mucosal immunity,
Expert Review of Vaccines, Vol.11, No.3, 367-379, 2012.

(要約): To develop protective immune responses against mucosal pathogens, the delivery route and adjuvants for vaccination are important. The host, however, strives to maintain mucosal homeostasis by responding to mucosal antigens with tolerance, instead of immune activation. Thus, induction of mucosal immunity through vaccination is a rather difficult task, and potent mucosal adjuvants, vectors or other special delivery systems are often used, especially in the elderly. By taking advantage of the common mucosal immune system, the targeting of mucosal dendritic cells and microfold epithelial cells may facilitate the induction of effective mucosal immunity. Thus, novel routes of immunization and antigen delivery systems also show great potential for the development of effective and safe mucosal vaccines against various pathogens. The purpose of this review is to introduce several recent approaches to induce mucosal immunity to vaccines, with an emphasis on mucosal tissue targeting, new immunization routes and delivery systems. Defining the mechanisms of mucosal vaccines is as important as their efficacy and safety, and in this article, examples of recent approaches, which will likely accelerate progress in mucosal vaccine development, are discussed.
(キーワード): Adjuvants, Immunologic / Animals / Drug Delivery Systems / Humans / Immune Tolerance / Immunity, Mucosal / Immunoglobulin A, Secretory / Vaccination / Vaccines
(出版サイトへのリンク): ● Publication site (DOI): 10.1586/erv.11.196
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 22380827; ● Summary page in Scopus @ Elsevier: 2-s2.0-84859085735

(DOI: 10.1586/erv.11.196, PubMed: 22380827, Elsevier: Scopus) Y. Fukuyama, D. Tokuhara, S. Sekine, Kosuke Kataoka, D. J. Markham, R. A. Irwin, H. G. Moon, Y. Tokuhara, . Ke. Fujihashi, J. Davydova, M. Yamamoto, S. R. Gilbert and K Fujihashi :
Notch-ligand expression by NALT dendritic cells regulates mucosal Th-1 and Th-2 type responses.,
Biochemical and Biophysical Research Communications, Vol.418, No.1, 6-11, 2012.

(要約): Our previous studies showed that an adenovirus (Ad) serotype 5 vector expressing Flt3 ligand (Ad-FL) as nasal adjuvant activates CD11c(+) dendritic cells (DCs) for the enhancement of antigen (Ag)-specific IgA antibody (Ab) responses. In this study, we examined the molecular mechanism for activation of CD11c(+) DCs and their roles in induction of Ag-specific Th1- and Th2-cell responses. Ad-FL activated CD11c(+) DCs expressed increased levels of the Notch ligand (L)-expression and specific mRNA. When CD11c(+) DCs from various mucosal and systemic lymphoid tissues of mice given nasal OVA plus Ad-FL were cultured with CD4(+) T cells isolated from non-immunized OVA TCR-transgenic (OT II) mice, significantly increased levels of T cell proliferative responses were noted. Furthermore, Ad-FL activated DCs induced IFN-γ, IL-2 and IL-4 producing CD4(+) T cells. Of importance, these APC functions by Ad-FL activated DCs were down-regulated by blocking Notch-Notch-L pathway. These results show that Ad-FL induces CD11c(+) DCs to the express Notch-ligands and these activated DCs regulate the induction of Ag-specific Th1- and Th2-type cytokine responses.
(キーワード): Adaptor Proteins, Signal Transducing / Animals / CD11c Antigen / Calcium-Binding Proteins / Cell Proliferation / Dendritic Cells / Immunity, Active / Immunity, Mucosal / Intercellular Signaling Peptides and Proteins / Intracellular Signaling Peptides and Proteins / Jagged-2 Protein / Ligands / Membrane Proteins / Mice / Mice, Inbred C57BL / Mice, Transgenic / Mucous Membrane / Receptors, Notch / Serrate-Jagged Proteins / Th1 Cells / Th2 Cells
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.bbrc.2011.12.046
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 22200492; ● Summary page in Scopus @ Elsevier: 2-s2.0-84856460586

(DOI: 10.1016/j.bbrc.2011.12.046, PubMed: 22200492, Elsevier: Scopus) Kosuke Kataoka, K. Fujihashi, Y. Terao, S. R. Gilbert, S. Sekine, R. Kobayashi, Y. Fukuyama, S. Kawabata and K. Fujihashi :
Oral-nasopharyngeal dendritic cells mediate T-independent IgA class switching on B-1 B cells,
PLoS ONE, Vol.6, No.9, e25396, 2011.

(要約): Native cholera toxin (nCT) as a nasal adjuvant was shown to elicit increased levels of T-independent S-IgA antibody (Ab) responses through IL-5- IL-5 receptor interactions between CD4+ T cells and IgA+ B-1 B cells in murine submandibular glands (SMGs) and nasal passages (NPs). Here, we further investigate whether oral-nasopharyngeal dendritic cells (DCs) play a central role in the induction of B-1 B cell IgA class switch recombination (CSR) for the enhancement of T cell-independent (TI) mucosal S-IgA Ab responses. High expression levels of activation-induced cytidine deaminase, Iα-Cμ circulation transcripts and Iμ-Cα transcripts were seen on B-1 B cells purified from SMGs and NPs of both TCRβ-/- mice and wild-type mice given nasal trinitrophenyl (TNP)-LPS plus nCT, than in the same tissues of mice given nCT or TNP-LPS alone. Further, DCs from SMGs, NPs and NALT of mice given nasal TNP-LPS plus nCT expressed significantly higher levels of a proliferation-inducing ligand (APRIL) than those in mice given TNP-LPS or nCT alone, whereas the B-1 B cells in SMGs and NPs showed elevated levels of transmembrane activator and calcium modulator cyclophilin ligand interactor (TACI) expression. Interestingly, high frequencies of IgA+ B-1 B cells were induced when peritoneal IgA- IgM+ B cells were stimulated with mucosal DCs from mice given nasal TNP-LPS plus nCT. Taken together, these findings show that nasal nCT plays a key role in the enhancement of mucosal DC-mediated TI IgA CSR by B-1 B cells through their interactions with APRIL and TACI.
(キーワード): Adaptor Proteins, Signal Transducing / Animals / B-Cell Activation Factor Receptor / B-Cell Maturation Antigen / B-Lymphocytes / Cholera Toxin / Dendritic Cells / Female / Gene Expression Regulation / Immunoglobulin A / Immunoglobulin Class Switching / Lipopolysaccharides / Mice / Mouth Mucosa / Nasopharynx / RNA, Messenger / Submandibular Gland / T-Lymphocytes / Tumor Necrosis Factor Ligand Superfamily Member 13
(出版サイトへのリンク): ● Publication site (DOI): 10.1371/journal.pone.0025396
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 21980444; ● Summary page in Scopus @ Elsevier: 2-s2.0-80053325722

(DOI: 10.1371/journal.pone.0025396, PubMed: 21980444, Elsevier: Scopus) Tselmeg Baatarjav, Kosuke Kataoka, Rebekah S. Gilbert, Yutaka Terao, Makoto Fukui, Masaki GOTO, Shigetada Kawabata, Masato Yamamoto, Kohtaro Fujihashi and Hiro-O Ito :
Mucosal immune features to phosphorylcholine by nasal Flt3 ligand cDNA-based vaccination,
Vaccine, Vol.29, No.34, 5747-5757, 2011.

(要約): Phosphorylcholine (PC) is an immunodominant epitope in some pathogens including Streptococcus pneumoniae and it is well-known that PC-specific antibodies (Abs) play a key role in the induction of protective immunity against pneumococcal infection. In this study, we examined whether nasal administration of DNA plasmid encoding Flt3 ligand gene (pFL) as a mucosal adjuvant plus PC-conjugated keyhole limpet hemocyanin (PC-KLH), would elicit PC-specific immune responses, and characterized mucosal immune responses to PC induced by this nasal vaccination. Nasal immunization with pFL plus PC-KLH enhanced induction of PC-specific IgA and IgM Abs in airway secretions when compared with mice given PC-KLH with or without empty plasmid gene (pORF) as controls; in addition to the mucosal immune responses, PC-specific immune responses in serum were also induced. Furthermore, the mucosal and serum IgA and IgM Abs in mice given pFL plus PC-KLH nasally, exhibited high-specificity for the PC molecule. Of interest, the PC-specific Abs bound dose-dependently to anti-T15 idiotype (AB1-2). Thus, the inhibition of S. pneumoniae colonization on the nasal cavity and lungs after nasal challenge with the live organism was significantly elicited in mice immunized with pFL plus PC-KLH compared to that of mice immunized with antigen with pORF. Taken together, these findings show that nasal administration of pFL with PC-KLH elicited T15-like anti-PC IgA and IgM Abs in the respiratory tracts, and further attenuated S. pneumoniae colonization on the respiratory tracts. Nasal administration of Flt3 ligand cDNA with PC may contribute to the development of nasal vaccination for prevention of S. pneumoniae infection.
(キーワード): Administration, Intranasal / Administration, Mucosal / Animals / Antibodies, Bacterial / Bacterial Vaccines / DNA, Complementary / Hemocyanin / Immunity, Mucosal / Immunoglobulin A / Immunoglobulin M / Membrane Proteins / Mice / Mice, Inbred C57BL / Phosphorylcholine / Plasmids / Pneumococcal Infections / Streptococcus pneumoniae / Vaccines, DNA
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.vaccine.2011.05.097
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 21683111; ● Summary page in Scopus @ Elsevier: 2-s2.0-79960560899

(DOI: 10.1016/j.vaccine.2011.05.097, PubMed: 21683111, Elsevier: Scopus) Kosuke Kataoka, Kohtaro Fujihashi, Keita Oma, Yoshiko Fukuyama, K Susan Hollingshead, Shinichi Sekine, Shigetada Kawabata, Hiro-O Ito, E David Briles and Kazunori Oishi :
Nasal Dendritic Cell Targeting Flt3 Ligand As A Safe Adjuvant Elicits Effective Protection Against Fatal Pneumococcal Pneumonia.,
Infection and Immunity, Vol.79, No.7, 2819-2828, 2011.

(要約): We have previously shown that pneumococcal surface protein A (PspA)-based vaccine containing DNA plasmid encoding the Flt3 ligand (FL) gene (pFL) as nasal adjuvant prevented nasal carriage of Streptococcus pneumoniae. In this study, we further investigated the safety and efficacy of this nasal vaccine for the induction of PspA-specific antibody (Ab) responses against lung infection with S. pneumoniae. C57BL/6 mice were nasally immunized with recombinant PspA/Rx1 (rPspA) plus pFL three times at weekly intervals. When dynamic translocation of pFL was initially examined, nasal pFL was taken-up by nasal dendritic cells (DCs) and epithelial cells (nECs), but not in the central nervous systems including olfactory nerve and epithelium. Of importance, nasal pFL induced FL protein synthesis with minimum levels of inflammatory cytokines in the nasal washes (NWs) and bronchoalveolar lavage fluid (BALF). NWs and BALF as well as plasma of mice given nasal rPspA plus pFL contained increased levels of rPspA-specific secretory-IgA and IgG Ab responses that are correlated with elevated numbers of CD8(+) and CD11b(+) DCs and IL-2 and IL-4 producing CD4(+) T cells in the nasopharyngeal-associated lymphoid tisses (NALT) and cervical lymph nodes (CLNs). The in vivo protection by rPspA-specific Abs was evident by reduced numbers of CFU in the lungs, airway secretions, and blood when mice were nasally challenged with Streptococcus pneumoniae WU2. Our findings show that nasal pFL is a safe and effective mucosal adjuvant for the enhancement of bacterial Ag (rPspA)-specific protective immunity through DC-induced Th2-type and IL-2 cytokine responses.
(キーワード): Adjuvants, Immunologic / Administration, Intranasal / Animals / Antibodies, Bacterial / Bacterial Proteins / Bronchoalveolar Lavage Fluid / CD4-Positive T-Lymphocytes / CD8-Positive T-Lymphocytes / 細胞質分裂 (cytokinesis) / Dendritic Cells / Epithelial Cells / Immunoglobulin A, Secretory / Immunoglobulin G / Membrane Proteins / Mice / Mice, Inbred C57BL / Nasal Cavity / Nasal Mucosa / Nasal Sprays / Plasmids / Pneumococcal Vaccines / Pneumonia, Pneumococcal / Recombinant Proteins / Streptococcus pneumoniae / Vaccines, Synthetic
(出版サイトへのリンク): ● Publication site (DOI): 10.1128/IAI.01360-10
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 21536790; ● Search Scopus @ Elsevier (PMID): 21536790; ● Search Scopus @ Elsevier (DOI): 10.1128/IAI.01360-10

(DOI: 10.1128/IAI.01360-10, PubMed: 21536790) Hiroshi Kido, Etsuhisa Takahashi, Kosuke Kataoka, Kazuyuki Fujii, Satoshi Suzuki, Kazuhiro Iwase and Chika Ito :
Attenuation of respiratory immune responses by antiviral neuraminidase inhibitor treatment and boost of mucosal immunoglobulin A response by co-administration of immuno- modulator clarithromycin in paediatric influenza.,
Influenza and Other Respiratory Viruses, Vol.5, No.1, 240-243, 2011.

(キーワード): Tamiflu, Infuenza virus, mucosal Immunology

R Kobayashi, T Kono, B A. Bolerjack, Y Fukuyama, R S. Gilbert, K Fujihashi, J Ruby, Kosuke Kataoka, M Wada, M Yamamoto and K Fujihashi :
Induction of IL-10-Producing CD4+ T Cells in Chronic Periodontitis.,
Journal of Dental Research, Vol.90, No.5, 653-658, 2011.

(要約): Precise immunological aspects of inflamed gingival mucosa remain to be elucidated in the murine experimental periodontitis model; therefore, we have characterized the mucosal immune cells in the inflamed gingiva of mice with alveolar bone reduction. Mice were orally infected with Porphyromonas gingivalis 15 times over 2 weeks. Gingival mononuclear cells (GMCs) were isolated from P. gingivalis-and sham-infected mice 1, 7, 15, and 30 days after the last infection. Although the greatest degree of periodontitis was seen in P. gingivalis-infected mice at 30 days after infection, the highest levels of IL-6 and TNF-α production were noted in the GMCs isolated 7 days after infection. Further, the frequency of RANKL(+)CD4(+) T-cells in GMCs of inflamed gingiva peaked 15 days after infection. Importantly, the number of Foxp3(+)CD4(+) CD25(+) regulatory T (Treg)-cells was increased only in the experimental group 30 days after infection. Thus, intracellular cytokine analysis revealed an increased number of IL-10-producing CD4(+) T-cells in inflamed gingiva when compared with the control group. These results suggest that there are potential roles for Treg cells during the chronic stage of periodontitis in the regulation of gingival inflammation and alveolar bone loss.
(出版サイトへのリンク): ● Publication site (DOI): 10.1177/0022034510397838
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 21335536; ● Search Scopus @ Elsevier (PMID): 21335536; ● Search Scopus @ Elsevier (DOI): 10.1177/0022034510397838

(DOI: 10.1177/0022034510397838, PubMed: 21335536) Makoto Fukui, Daisuke Hinode, Masaaki Yokoyama, Masami Yoshioka, Kosuke Kataoka and Hiro-O Ito :
Levels of salivary stress markers in patients with anxiety about halitosis,
Archives of Oral Biology, Vol.55, No.11, 842-847, 2010.

(要約): To investigate the relationship between salivary stress markers and mental stress states in patients complaining of oral malodour. The utility of the salivary stress markers in assessment of mental conditions of those patients was also investigated. The study population included 74 patients, aged 20-59 years, who complained of oral malodour and were referred to the Breath Odor Clinic at Tokushima University Hospital. Patients were classified into two groups, genuine halitosis (GH) and psychosomatic halitosis (PH), according to the results of organoleptic rating measurement. All patients were subjected to examination by the Cornell Medical Index (CMI) Health Questionnaire. Resting saliva was collected and levels of salivary IgA, cortisol and chromogranin A were determined by ELISA. Twenty-three volunteers not complaining of halitosis were included as the control group. Kruskal-Wallis test and Mann-Whitney's U-test were used for statistical analysis. A significant increase was observed in the concentrations of salivary cortisol in the PH group as compared with GH and control groups (p<0.05). Concentrations of IgA and chromogranin A in saliva were not significantly different among the three groups. In addition, higher salivary cortisol concentrations were found in CMI scale III and IV (tendency towards neurosis) than in scale I and II (normal) (p<0.05). Since salivary cortisol reflects a status of chronic stress condition, psychosomatic halitosis might be closely related to this state of chronic stress. Determination of cortisol levels in saliva may provide useful information for evaluating the mental status of patients complaining of halitosis.
(キーワード): Adult / Anxiety / Biological Markers / Case-Control Studies / Chromogranin A / Enzyme-Linked Immunosorbent Assay / Female / Halitosis / Humans / Hydrocortisone / Immunoglobulin A / Male / Middle Aged / Psychophysiologic Disorders / Questionnaires / Saliva / Statistics, Nonparametric
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.archoralbio.2010.07.014
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 20807658; ● Search Scopus @ Elsevier (PMID): 20807658; ● Search Scopus @ Elsevier (DOI): 10.1016/j.archoralbio.2010.07.014

(DOI: 10.1016/j.archoralbio.2010.07.014, PubMed: 20807658) Yoshiko Fukuyama, Janice D. King, Kosuke Kataoka, Ryoki Kobayashi, Rebekah S. Gilbert, Kazunori Oishi, Susan K. Hollingshead, David E. Briles and Kohtaro Fujihashi :
Secretory-IgA antibodies play an important role in the immunity to Streptococcus pneumoniae.,
The Journal of Immunology, Vol.185, No.3, 1755-1762, 2010.

(要約): This study was designed to investigate whether secretory-IgA (S-IgA) Abs induced by a pneumococcal surface protein A (PspA)-based nasal vaccine are necessary for prevention of streptococcal colonization. Mice nasally immunized with PspA plus a plasmid expressing Flt3 ligand (pFL) cDNA as a mucosal adjuvant showed significantly higher levels of PspA-specific S-IgA and IgG Ab responses in both plasma and nasal washes when compared with naive mice. Although IgA(-/-) mice given nasal PspA plus pFL had significantly high levels of PspA-specific IgG Abs, high numbers of CFUs were detected in nasal washes and nasal passages. In contrast, vaccinated wild-type mice showed essentially no bacteria in the nasal cavity. Further, a nasal vaccine consisting of PspA plus pFL effectively reduced pre-existing Streptococcus pneumoniae in the nasal cavity. These results show that PspA-based vaccine-induced specific S-IgA Abs play a necessary role in the regulation of S. pneumoniae colonization in the nasal cavity.
(キーワード): Adjuvants, Immunologic / Administration, Intranasal / Animals / Antibodies, Bacterial / Bacterial Proteins / Bacterial Vaccines / Cells, Cultured / Colony Count, Microbial / Female / Immunity, Innate / Immunoglobulin A, Secretory / Membrane Proteins / Mice / Mice, Inbred C57BL / Mice, Knockout / Streptococcal Infections
(出版サイトへのリンク): ● Publication site (DOI): 10.4049/jimmunol.1000831
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 20585031; ● Search Scopus @ Elsevier (PMID): 20585031; ● Search Scopus @ Elsevier (DOI): 10.4049/jimmunol.1000831

(DOI: 10.4049/jimmunol.1000831, PubMed: 20585031) Etsuhisa Takahashi, Kosuke Kataoka, Kazuyuki Fujii, Junji Chida, Dai Mizuno, Makoto Fukui, Hiro-O Ito, Kohtaro Fujihashi and Hiroshi Kido :
Attenuation of inducible respiratory immune responses by oseltamivir treatment in mice infected with influenza A virus.,
Microbes and Infection, Vol.12, No.10, 778-783, 2010.

(要約): The antiviral neuraminidase inhibitor oseltamivir (OSV) is widely used to suppress viral replication in the treatment of influenza. Here, we report that OSV administration significantly suppressed respiratory mucosal secretory IgA responses with respect to antigen (Ag)-specific antibody (Ab) production and also the induction of Ag-specific IgA Ab-forming cells, but not systemic IgG responses, in weanling mice as a model of pediatric influenza. Neutralizing activities of the airway fluids in oral OSV-treated mice were significantly less than those of sham-treated mice. Our findings suggest the risk of re-infection in patients showing a low mucosal response following OSV treatment.
(キーワード): Animals / Antibodies, Viral / Antiviral Agents / Female / Immunity, Mucosal / Immunoglobulin A / Immunoglobulin G / Immunosuppression / Immunosuppressive Agents / Influenza A virus / Mice / Mice, Inbred BALB C / Orthomyxoviridae Infections / Oseltamivir
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.micinf.2010.04.013
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 20452454; ● Search Scopus @ Elsevier (PMID): 20452454; ● Search Scopus @ Elsevier (DOI): 10.1016/j.micinf.2010.04.013

(DOI: 10.1016/j.micinf.2010.04.013, PubMed: 20452454) Hidetaka Nakagaki, Shinichi Sekine, Yutaka Terao, Masahiro Toe, Muneo Tanaka, Hiro-O Ito, Shigetada Kawabata, Satoshi Shizukuishi, Kohtaro Fujihashi and Kosuke Kataoka :
Fusobacterium nucleatum envelope protein FomA is immunogenic and binds to the salivary statherin-derived peptide.,
Infection and Immunity, Vol.78, No.3, 1185-1192, 2010.

(要約): We have previously shown that one of the minimal active regions of statherin, a human salivary protein, for binding to Fusobacterium nucleatum is a YQPVPE amino acid sequence. In this study, we identified the FomA protein of F. nucleatum, which is responsible for binding to the statherin-derived YQPVPE peptide. Overlay analysis showed that a 40-kDa protein of the F. nucleatum cell envelope (40-kDa CE) specifically bound to the YQPVPE peptide. The equilibrium association constant between the affinity-purified 40-kDa CE and the YQPVPE peptide was 4.30 x 10(6). Further, the purity and amino acid sequence analyses of the purified 40-kDa CE revealed approximately 98.7% (wt/wt) purity and a high degree of homology with FomA, a major porin protein of F. nucleatum. Thus, a FomA-deficient mutant failed to bind to the YQPVPE peptide. In addition, increased levels of a FomA-specific mucosal IgA antibody (Ab) and plasma IgG and IgA Abs were seen only in mice immunized nasally with cholera toxin (CT) and the purified 40-kDa FomA protein. Interestingly, saliva from mice that received FomA plus CT as a mucosal adjuvant nasally prevented in vitro binding of F. nucleatum to statherin-coated polyvinyl chloride plates. Taken together, these results suggest that induction of specific immunity to the 40-kDa FomA protein of F. nucleatum, which specifically binds to the statherin-derived peptide, may be an effective tool for preventing the formation of F. nucleatum biofilms in the oral cavity.
(キーワード): Amino Acid Sequence / Animals / Antibodies, Bacterial / Bacterial Outer Membrane Proteins / Female / Fusobacterium nucleatum / Gene Deletion / Humans / Immunoglobulin A / Immunoglobulin G / Kinetics / Mice / Mice, Inbred C57BL / Molecular Sequence Data / Molecular Weight / Mucous Membrane / Protein Binding / Protein Interaction Mapping / Salivary Proteins and Peptides
(出版サイトへのリンク): ● Publication site (DOI): 10.1128/IAI.01224-09
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 20008529; ● Search Scopus @ Elsevier (PMID): 20008529; ● Search Scopus @ Elsevier (DOI): 10.1128/IAI.01224-09

(DOI: 10.1128/IAI.01224-09, PubMed: 20008529) Kosuke Kataoka and Kohtaro Fujihashi :
Dendritic cell-targeting DNA-based mucosal adjuvants for the development of mucosal vaccines.,
Expert Review of Vaccines, Vol.8, No.9, 1183-1193, 2009.

(要約): In order to establish effective mucosal immunity against various mucosal pathogens, vaccines must be delivered via the mucosal route and contain effective adjuvant(s). Since mucosal adjuvants can simply mix with the antigen, it is relatively easy to adapt them for different types of vaccine development. Even in simple admixture vaccines, the adjuvant itself must be prepared without any complications. Thus, CpG oligodeoxynucleotides or plasmids encoding certain cDNA(s) would be potent mucosal adjuvant candidates when compared with other substances that can be used as mucosal adjuvants. The strategy of a DNA-based mucosal adjuvant facilitates the targeting of mucosal dendritic cells, and thus is an effective and safe approach. It would also provide great flexibility for the development of effective vaccines for various mucosal pathogens.
(キーワード): Adjuvants, Immunologic / DNA (DNA) / Dendritic Cells / Humans / Immunity, Mucosal / Immunoglobulin A, Secretory / Plasmids / Vaccines
(出版サイトへのリンク): ● Publication site (DOI): 10.1586/erv.09.80
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 19722892; ● Search Scopus @ Elsevier (PMID): 19722892; ● Search Scopus @ Elsevier (DOI): 10.1586/erv.09.80

(DOI: 10.1586/erv.09.80, PubMed: 19722892) 横山正明, 福井誠, 増田かなめ, 髙松夏子, 岡田寿朗, 武部裕光, 片岡宏介, 伊藤博夫 :
リアルタイム定量PCR(qPCR)法による唾液中の総細菌数の測定口腔清潔度の指標としての試み,
口腔衛生学会雑誌, Vol.59, No.3, 183-189, 2009年.

(要約): 口腔清潔度の指標としては,歯面への歯垢の付着度を測定する方法が一般的であるが,診査や記録等の人材的,時間的負担を要することから,集団歯科健診で用いられることは少ない.集団歯科健診においてう蝕や歯周疾患,口臭症のリスクを評価するために,簡便かつ有効な口腔清潔度の評価法の開発が望まれている.リアルタイム定量PCR(qPCR)法による唾液中の総細菌数の測定は,検体の採取や保管が容易で多検体の一括処理が可能であることから,本目的に合致する有望な測定法であると考えられる.本研究では,qPCR法を用いた唾液中の総細菌数の測定が口腔清潔度の評価法として使用できるかどうか検討を行った.5名のボランティアから,ブラッシング中断時と再開後の2回,刺激唾液を採取し,唾液中の総細菌数をqPCR法により測定したところ,Debris Index,O'LearyのPCR値との間に相関は示されなかったものの,ブラッシング再開後では,中断時に比べ,有意に減少した.81名の被験者から4ヵ月の間隔を空けて2回刺激唾液を採取し,唾液中の総細菌数をqPCR法により測定したところ,前後の間に有意な正の相関を認めた.以上の結果より,qPCR法によって唾液中の総細菌数を測定することが可能であることが示された.本法は非常に簡便であることから,今後,口腔清潔度を検討する分野において応用できる可能性が考えられる.
(キーワード): *Polymerase Chain Reaction
(文献検索サイトへのリンク): ● CiNii @ 国立情報学研究所 (CRID): 1390282679981008896

(CiNii: 1390282679981008896) Hideki Nagata, Yoshika Inagaki, Muneo Tanaka, Miki Ojima, Kosuke Kataoka, Masae Kuboniwa, Nobuko Nishida, Katsumasa Shimizu, Kenji Osawa and Satoshi Shizukuishi :
Effect of eucalyptus-extract chewing gum on periodontal health: Double blind, randomized trial.,
Journal of Periodontology, Vol.79, No.8, 1378-1385, 2008.

(要約): Studies in vitro showed that eucalyptus extracts possess antibacterial activity against cariogenic and periodontopathic bacteria; however, the clinical effects with respect to periodontal health in humans remain unproven. The objective of this study was to evaluate the effect of chewing gum containing eucalyptus extract on periodontal health in a double-masked, randomized, controlled trial. Healthy humans with gingivitis but not deep periodontal pockets were randomly assigned to the following groups: high-concentration group (n=32): use of 0.6% eucalyptus extract chewing gum for 12 weeks (90 mg/day); low-concentration group (n=32): use of 0.4% eucalyptus extract chewing gum for 12 weeks (60 mg/day); and placebo group (n=33): use of chewing gum without eucalyptus extract for 12 weeks. Plaque accumulation (PLA), gingival index (GI), bleeding on probing (BOP), periodontal probing depth (PD), and clinical attachment level (CAL) were measured at weeks 0, 4, 8, 12, and 14. Significance was analyzed with repeated-measures two-way analysis of variance followed by the Games-Howell pairwise comparison test. The interaction between the effects of eucalyptus extract chewing gum and the intake period was statistically significant for PLA, GI, BOP, and PD but not for CAL. The low- and high-concentration groups exhibited statistically significant (P <0.05) improvements compared to the placebo group for PLA, GI, BOP, and PD. Eucalyptus extract chewing gum had a significant effect on PLA, GI, BOP, and PD. The use of eucalyptus extract chewing gum may promote periodontal health.
(キーワード): Adult / Chewing Gum / Dental Plaque / Dental Plaque Index / Dental Scaling / Double-Blind Method / Eucalyptus / Female / Gingival Hemorrhage / Gingivitis / Humans / Male / Middle Aged / Periodontal Attachment Loss / Periodontal Index / Periodontal Pocket / Phytotherapy / Placebos / Plant Extracts
(出版サイトへのリンク): ● Publication site (DOI): 10.1902/jop.2008.070622
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 18672986; ● Search Scopus @ Elsevier (PMID): 18672986; ● Search Scopus @ Elsevier (DOI): 10.1902/jop.2008.070622

(DOI: 10.1902/jop.2008.070622, PubMed: 18672986) Tatsuya Fukuiwa, Shinichi Sekine, Ryoki Kobayashi, Hideaki Suzuki, Kosuke Kataoka, Rebekah S. Gilbert, Yuichi Kurono, Prosper N. Boyaka, Arthur M. Krieg, Jerry R. McGhee and Kohtaro Fujihashi :
A combination of Flt3 Ligand cDNA and CpG ODN as nasal adjuvants elicits NALT dendritic cells for prolonged mucosal immunity.,
Vaccine, Vol.26, No.37, 4849-4859, 2008.

(要約): We explore cellular and molecular mechanisms of nasal adjuvant of a combination of a plasmid encoding the Flt3 ligand cDNA (pFL) and CpG oligodeoxynucleotides (CpG ODN). The double DNA adjuvant given with OVA maintained prolonged OVA-specific secretory IgA (S-IgA) Ab responses in external secretions for more than 25 weeks after the final immunization. Further, both Th1- and Th2-type cytokine responses were induced by this combined adjuvant regimen. The frequencies of plasmacytoid DCs (pDCs) and CD8(+) DCs were significantly increased in nasopharyngeal-associated lymphoreticular tissue (NALT) of mice given the combined adjuvant. Importantly, when we examined adjuvanticity of pFL plus CpG ODN in 2-year-old mice, significant levels of mucosal IgA Ab responses were also induced. These results demonstrate that nasal delivery of a combined DNA adjuvant offers an attractive possibility for the development of an effective mucosal vaccine for the elderly.
(キーワード): Adjuvants, Immunologic / Administration, Intranasal / Animals / 細胞質分裂 (cytokinesis) / DNA, Complementary / Dendritic Cells / Female / Immunoglobulin A / Membrane Proteins / Mice / Mice, Inbred BALB C / Nasal Mucosa / Nasopharynx / Oligodeoxyribonucleotides / Ovalbumin / Plasmids
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.vaccine.2008.06.091
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 18625280; ● Search Scopus @ Elsevier (PMID): 18625280; ● Search Scopus @ Elsevier (DOI): 10.1016/j.vaccine.2008.06.091

(DOI: 10.1016/j.vaccine.2008.06.091, PubMed: 18625280) Shinichi Sekine, Kosuke Kataoka, Yoshiko Fukuyama, Yasuo Adachi, Julia Davydova, Masato Yamamoto, Ryoki Kobayashi, Keiko Fujihashi, Hideaki Suzuki, David Curiel, Satoshi Shizukuishi, Jerry McGhee and Kohtaro Fujihashi :
A novel adenovirus expressing Flt3 ligand enhances mucosal immunity by inducing mature NALT dendritic cell migration.,
The Journal of Immunology, Vol.180, No.12, 8126-8134, 2008.

(要約): Previously, we showed that nasal administration of a naked cDNA plasmid expressing Flt3 ligand (FL) cDNA (pFL) enhanced CD4(+) Th2-type, cytokine-mediated mucosal immunity and increased lymphoid-type dendritic cell (DC) numbers. In this study, we investigated whether targeting nasopharyngeal-associated lymphoreticular tissue (NALT) DCs by a different delivery mode of FL, i.e., an adenovirus (Ad) serotype 5 vector expressing FL (Ad-FL), would provide Ag-specific humoral and cell-mediated mucosal immunity. Nasal immunization of mice with OVA plus Ad-FL as mucosal adjuvant elicited high levels of OVA-specific Ab responses in external secretions and plasma as well as significant levels of OVA-specific CD4(+) T cell proliferative responses and OVA-induced IFN-gamma and IL-4 production in NALT, cervical lymph nodes, and spleen. We also observed higher levels of OVA-specific CTL responses in the spleen and cervical lymph nodes of mice given nasal OVA plus Ad-FL than in mice receiving OVA plus control Ad. Notably, the number of CD11b(+)CD11c(+) DCs expressing high levels of costimulatory molecules was preferentially increased. These DCs migrated from the NALT to mucosal effector lymphoid tissues. Taken together, these results suggest that the use of Ad-FL as a nasal adjuvant preferentially induces mature-type NALT CD11b(+)CD11c(+) DCs that migrate to effector sites for subsequent CD4(+) Th1- and Th2-type cytokine-mediated, Ag-specific Ab and CTL responses.
(キーワード): Adenoviridae / Adjuvants, Immunologic / Administration, Intranasal / Animals / Cell Differentiation / Cell Line / Cell Line, Tumor / Cell Movement / Dendritic Cells / Female / Genetic Vectors / Humans / Immunity, Mucosal / Lymphoid Tissue / Membrane Proteins / Mice / Mice, Inbred C57BL / Mononuclear Phagocyte System / Nasopharynx / fms-Like Tyrosine Kinase 3
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 18523277; ● Search Scopus @ Elsevier (PMID): 18523277

(PubMed: 18523277) Hideaki Suzuki, Shinichi Sekine, Kosuke Kataoka, David W. Pascual, Massimo Maddaloni, Ryoki Kobayashi, Keiko Fujihashi, Haruo Kozono, Jerry R. McGhee and Kohtaro Fujihashi :
Ovalbumin-protein sigma 1 M-cell targeting facilitates oral tolerance with reduction of antigen-specific CD4+ T cells.,
Gastroenterology, Vol.135, No.3, 917-925, 2008.

(要約): BACKGROUND & AIMS: The follicle-associated epithelium (FAE) plays key roles in antigen uptake and subsequent induction of mucosal immunity. In this study, we examined whether M-cell targeting using a protein antigen (Ag) delivery system would induce oral tolerance instead of enhancement of Ag-specific mucosal antibody (Ab) responses. METHODS: Mice were fed different doses of a recombinant protein sigma 1 of reovirus genetically conjugated to ovalbumin (OVA-psigma1), psigma1 only, or phosphate-buffered saline (PBS) before oral challenge with OVA plus cholera toxin as mucosal adjuvant. OVA-specific Ab and CD4-positive (CD4(+)) T-cell responses were determined. RESULTS: A low dose of OVA-psigma1 reduced anti-OVA Ab and CD4(+) T-cell responses in both mucosal and systemic lymphoid tissues. OVA/MHC I-A(d) tetramer staining showed that the numbers of OVA-specific CD4(+) T cells were significantly reduced in lamina propria of mice fed OVA-psigma1 than those fed psigma1 only or PBS only. In fact, Foxp3 expressing CD25(+) CD4(+) T cells were markedly increased in this tissue. Nonetheless, CD25(+) CD4(+) T cells from the spleen, mesenteric lymph nodes, and Peyer's patches of orally tolerized mice showed increased transforming growth factor beta1 (TGF-beta1) and interleukin-10 (IL-10) production compared with nontolerized mice. CONCLUSIONS: These results show that an FAE M-cell targeting protein Ag delivery system facilitates oral tolerance induction because of a reduction in Ag-specific CD4(+) T cells and increased levels of TGF-beta1 and IL-10 producing, CD25(+) CD4(+) regulatory T cells in both systemic and mucosal lymphoid tissues.
(キーワード): Administration, Oral / Animals / Antibody Formation / CD4-Positive T-Lymphocytes / Capsid Proteins / Epitopes / Immune Tolerance / Immunity, Mucosal / Immunization / Interferon-gamma / Lymphoid Tissue / Mice / Mice, Inbred BALB C / Mouth Mucosa / Ovalbumin / Transforming Growth Factor beta1
(出版サイトへのリンク): ● Publication site (DOI): 10.1053/j.gastro.2008.05.037
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 18565333; ● Search Scopus @ Elsevier (PMID): 18565333; ● Search Scopus @ Elsevier (DOI): 10.1053/j.gastro.2008.05.037

(DOI: 10.1053/j.gastro.2008.05.037, PubMed: 18565333) Tomomi Hashizume, Fumiki Momoi, Tomoko Kurita-Ochiai, Shuichi Kaminogawa, Akira Hosono, Kosuke Kataoka, Noriko Shinozaki-Kuwahara, Mi-Na Kweon and Masafumi Yamamoto :
Isolated lymphoid follicles are not IgA inductive sites for recombinant Salmonella.,
Biochemical and Biophysical Research Communications, Vol.360, No.2, 388-393, 2007.

(要約): In this study, we investigated whether isolated lymphoid follicles (ILF) play a role in the regulation of intestinal IgA antibody (Ab) responses. The transfer of wild type (WT) bone marrow (BM) to lymphotoxin-alpha-deficient (LTalpha(-/-)) mice resulted in the formation of mature ILF containing T cells, B cells, and FDC clusters in the absence of mesenteric lymph nodes and Peyer's patches. Although the ILF restored total IgA Abs in the intestine, antigen (Ag)-specific IgA responses were not induced after oral immunization with recombinant Salmonella expressing fragment C of tetanus toxin. Moreover, Ag-specific cell proliferation was not detected in the ILF. Interestingly, no IgA anti-LPS Abs were detected in the fecal extracts of LTalpha(-/-) mice reconstituted with WT BM. On the basis of these findings, ILF can be presumed to play a role in the production of IgA Abs, but lymphoid nodules are not inductive sites for the regulation of Ag-specific intestinal IgA responses to recombinant Salmonella.
(キーワード): Animals / Immunoglobulin A / Intestine, Small / Lymphoid Tissue / Lymphotoxin-alpha / Mice / Mice, Inbred C57BL / Recombination, Genetic / Salmonella typhimurium
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.bbrc.2007.06.096
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 17606222; ● Search Scopus @ Elsevier (PMID): 17606222; ● Search Scopus @ Elsevier (DOI): 10.1016/j.bbrc.2007.06.096

(DOI: 10.1016/j.bbrc.2007.06.096, PubMed: 17606222) Kosuke Kataoka, Keiko Fujihashi, Shinichi Sekine, Tatsuya Fukuiwa, Ryoki Kobayashi, Hideaki Suzuki, Hideki Nagata, Kiyoshi Takatsu, Satoshi Shizukuishi, Jerry R. McGhee and Kohtaro Fujihashi :
Nasal cholera toxin elicits IL-5 and IL-5 receptor α-chain expressing B-1a B cells for innate mucosal IgA antibody responses.,
The Journal of Immunology, Vol.178, No.10, 6058-6065, 2007.

(要約): In this study, we examine whether native cholera toxin (nCT) as a mucosal adjuvant can support trinitrophenyl (TNP)-LPS-specific mucosal immune responses. C57BL/6 mice were given nasal TNP-LPS in the presence or absence of nCT. Five days later, significantly higher levels of TNP-specific mucosal IgA Ab responses were induced in the nasal washes, saliva, and plasma of mice given nCT plus TNP-LPS than in those given TNP-LPS alone. High numbers of TNP-specific IgA Ab-forming cells were also detected in mucosal tissues such as the nasal passages (NPs), the submandibular glands (SMGs), and nasopharyngeal-associated lymphoreticular tissue of mice given nCT. Flow cytometric analysis showed that higher numbers of surface IgA+, CD5+ B cells (B-1a B cells) in SMGs and NPs of mice given nasal TNP-LPS plus nCT than in those given TNP-LPS alone. Furthermore, increased levels of IL-5R alpha-chain were expressed by B-1a B cells in SMGs and NPs of mice given nasal TNP-LPS plus nCT. Thus, CD4+ T cells from these mucosal effector lymphoid tissues produce high levels of IL-5 at both protein and mRNA levels. When mice were treated with anti-IL-5 mAb, significant reductions in TNP-specific mucosal IgA Ab responses were noted in external secretions. These findings show that nasal nCT as an adjuvant enhances mucosal immune responses to a T cell-independent Ag due to the cross-talk between IL-5Ralpha+ B-1a B cells and IL-5-producing CD4+ T cells in the mucosal effector lymphoid tissues.
(キーワード): Adjuvants, Immunologic / Animals / Antigens, T-Independent / B-Lymphocyte Subsets / Cholera Toxin / Epitopes, B-Lymphocyte / Female / Forkhead Transcription Factors / 自然免疫 (innate immunity) / Immunity, Mucosal / Immunoglobulin A / Interleukin-5 / Interleukin-5 Receptor alpha Subunit / Lipopolysaccharides / Mice / Mice, Inbred C57BL / Nasal Mucosa / Submandibular Gland
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 17475830; ● Search Scopus @ Elsevier (PMID): 17475830

(PubMed: 17475830) Miyuki Kibayashi, Muneo Tanaka, Nobuko Nishida, Masae Kuboniwa, Kosuke Kataoka, Hideki Nagata, Kunio Nakayama, Kanehisa Morimoto and Satoshi Shizukuishi :
Longitudinal study of the association between smoking as a periodontitis risk and salivary biomarkers related to periodontitis.,
Journal of Periodontology, Vol.78, No.5, 859-867, 2007.

(要約): BACKGROUND: Insufficient data exist regarding the long-term influence of lifestyle factors including smoking on periodontal health. The objective of this study was to examine the prospective association between smoking and periodontal disease progression and the effects of smoking on salivary biomarkers related to periodontitis. METHODS: Probing depth (PD) was measured at health checkups of workers in 1999 and 2003; additionally, lifestyle information was obtained through a questionnaire. In 2003, 219 of 256 (86%) workers examined at baseline completed PD measurements; saliva samples were also collected. Change in PD was used for assessment of periodontitis progression when three or more sites displayed an increase of >or=2 mm over 4 years. Salivary biomarker levels were determined by real-time polymerase chain reaction and enzyme assay. Statistical methods included bivariate and multivariate regression analyses. RESULTS: In the multiple logistic model, in which lifestyle-related factors served as independent variables, significant variables were current smoking and hours of sleep; respective odds ratios were 2.3 and 2.1. Additionally, 38.5% of periodontal disease progression was attributable to current smoking. Moreover, pack-years of smoking showed a dose-response relationship with disease progression. Levels of salivary markers including prostaglandin E(2), lactoferrin, albumin, aspartate aminotransferase, lactate dehydrogenase, and alkaline phosphatase were significantly lower in current smokers than in non-current smokers. However, no meaningful differences in the proportions of six periodontal pathogens were observed between current and non-current smokers. CONCLUSIONS: Smoking exerted the greatest influence on periodontitis risk among lifestyle factors. Smoking may suppress the host-defense system, which may promote periodontal disease progression.
(キーワード): Adolescent / Adult / Albumins / Alkaline Phosphatase / Aspartate Aminotransferases / Bacteroidaceae / Biological Markers / Dental Health Surveys / Dinoprostone / Disease Progression / Female / Humans / 日本 (Japan) / L-Lactate Dehydrogenase / Lactoferrin / ライフスタイル (lifestyle) / Logistic Models / Longitudinal Studies / Male / Middle Aged / 歯周病 (periodontitis) / Population Surveillance / Regression Analysis / Risk Factors / Saliva / Sex Factors / 喫煙 (smoking)
(出版サイトへのリンク): ● Publication site (DOI): 10.1902/jop.2007.060292
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 17470019; ● Search Scopus @ Elsevier (PMID): 17470019; ● Search Scopus @ Elsevier (DOI): 10.1902/jop.2007.060292

(DOI: 10.1902/jop.2007.060292, PubMed: 17470019) Yukari Hagiwara, Yuki I. Kawamura, Kosuke Kataoka, Bibi Rahima, Raymond J. Jackson, Katsuhiro Komase, Taeko Dohi, Prosper N. Boyaka, Yoshifumi Takeda, Hiroshi Kiyono, Jerry R. McGhee and Kohtaro Fujihashi :
A second generation of double mutant cholera toxin adjuvants: enhanced immunity without intracellular trafficking.,
The Journal of Immunology, Vol.177, No.5, 3045-3054, 2006.

(要約): Nasal application of native cholera toxin (nCT) as a mucosal adjuvant has potential toxicity for the CNS through binding to GM1 gangliosides in the olfactory nerves. Although mutants of cholera toxin (mCTs) have been developed that show mucosal adjuvant activity without toxicity, it still remains unclear whether these mCTs will induce CNS damage. To help overcome these concerns, in this study we created new double mutant CTs (dmCTs) that have two amino acid substitutions in the ADP-ribosyltransferase active center (E112K) and COOH-terminal KDEL (E112K/KDEV or E112K/KDGL). Confocal microscopic analysis showed that intracellular localization of dmCTs differed from that of mCTs and nCTs in intestinal epithelial T84 cells. Furthermore, both dmCTs exhibited very low toxicity in the Y1 cell assay and mouse ileal loop tests. When mucosal adjuvanticity was examined, both dmCTs induced enhanced OVA-specific immune responses in both mucosal and systemic lymphoid tissues. Interestingly, although both dmCT E112K/KDEV and dmCT E112K/KDGL showed high Th2-type and significant Th1-type cytokine responses by OVA-specific CD4+ T cells, dmCT E112K/KDEV exhibited significantly lower Th1-type cytokine responses than did nCT and dmCT E112K/KDGL. These results show that newly developed dmCTs retain strong biological adjuvant activity without CNS toxicity.
(キーワード): Adjuvants, Immunologic / Animals / Antibodies / CD4-Positive T-Lymphocytes / Cell Proliferation / 中枢神経系 (central nervous system) / Cholera Toxin / 細胞質分裂 (cytokinesis) / 小胞体 (endoplasmic reticulum) / Golgi Apparatus / Immunity, Mucosal / Mice / Mice, Inbred C57BL / Mutation / Olfactory Bulb / Ovalbumin / Protein Transport
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 16920941; ● Search Scopus @ Elsevier (PMID): 16920941

(PubMed: 16920941) Nobuko Nishida, Yumiko Yamamoto, Muneo Tanaka, Kazuhiko Maeda, Kosuke Kataoka, Kunio Nakayama, Kanehisa Morimoto and Satoshi Shizukuishi :
Association between passive smoking and salivary markers related to periodontitis.,
Journal of Clinical Periodontology, Vol.33, No.10, 717-723, 2006.

(要約): OBJECTIVES: The mechanism of passive smoking in terms of development of periodontitis has not been investigated. This study examined the effect of passive smoking on salivary markers related to periodontitis. METHODS: Periodontal status was evaluated on the basis of probing pocket depth and clinical attachment level in 273 workers. Salivary marker levels were determined by enzyme assay including enzyme-linked immunosorbent assay. Six periodontal pathogens in saliva were assessed using real-time PCR methodology. Non-, passive and active smokers were defined as subjects exhibiting salivary cotinine levels of 0 (53 subjects), 1-7 (118) and > or = 8 ng/ml (102). RESULTS: Levels of salivary markers, including IL-1beta, lactoferrin, albumin and aspartate aminotransferase (AST), were elevated significantly in passive smokers relative to non-smokers. Additionally, these marker levels, with the exception of IL-1beta, decreased significantly in active smokers in comparison with passive smokers. However, no meaningful differences in percentages of periodontal pathogens were observed between non- and passive smokers. Multiple linear regression analyses were performed for each marker utilizing age, gender, cotinine level and periodontal status as independent variables. IL-1beta, albumin and AST were independently associated with cotinine level. CONCLUSION: Passive smoke exposure leads to elevation of IL-1beta, albumin and AST levels in saliva.
(キーワード): Adolescent / Adult / Albumins / Aspartate Aminotransferases / Biological Markers / Cotinine / Female / Humans / Interleukin-1beta / Lactoferrin / Male / Middle Aged / Periodontal Attachment Loss / Periodontal Index / Periodontal Pocket / 歯周病 (periodontitis) / Porphyromonas gingivalis / Prevotella intermedia / Prevotella nigrescens / Saliva / 喫煙 (smoking) / Tobacco Smoke Pollution
(出版サイトへのリンク): ● Publication site (DOI): 10.1111/j.1600-051X.2006.00982.x
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 16889628; ● Search Scopus @ Elsevier (PMID): 16889628; ● Search Scopus @ Elsevier (DOI): 10.1111/j.1600-051X.2006.00982.x

(DOI: 10.1111/j.1600-051X.2006.00982.x, PubMed: 16889628) H Nagata, Y Inagaki, Y Yamamoto, K Maeda, Kosuke Kataoka, K Osawa and S Shizukuishi :
Inhibitory effects of macrocarpals on the biological activity of Porphyromonas gingivalis and other periodontopathic bacteria.,
Oral Microbiology and Immunology, Vol.21, No.3, 159-163, 2006.

(要約): BACKGROUND/AIMS: Macrocarpals, which are phloroglucinol derivatives contained in eucalyptus leaves, exhibit antimicrobial activity against a variety of bacteria including oral bacteria. This study examined effects of macrocarpals A, B, and C on periodontopathic bacteria, especially Porphyromonas gingivalis. METHODS: Macrocarpals A, B, and C were purified from a 60% ethanol-extract of Eucalyptus globules leaves. To investigate antibacterial activity, representative periodontopathic bacteria were cultured in media with or without various amounts of macrocarpals; subsequently, the optical density at 660 nm was measured. Macrocarpal inhibition of P. gingivalis Arg- and Lys-specific proteinases was assessed by spectrofluorophotometric assay and sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis. The effect of macrocarpals on P. gingivalis binding to saliva-coated hydroxyapatite beads was examined with (3)H-labeled P. gingivalis. RESULTS: Growth of P. gingivalis was inhibited more strongly than growth of Prevotella intermedia or Prevotella nigrescens and Treponema denticola by macrocarpals, however, Actinobacillus actinomycetemcomitans and Fusobacterium nucleatum were much more resistant. Macrocarpals inhibited P. gingivalis Arg- and Lys-specific proteinases in a dose-dependent manner. The enzyme-inhibitory effect of macrocarpals was confirmed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis in which hemoglobin degradation by P. gingivalis proteinase was inhibited by macrocarpals. P. gingivalis binding to saliva-coated hydroxyapatite beads was also strongly attenuated by macrocarpals. CONCLUSIONS: Macrocarpals A, B and C demonstrated antibacterial activity against periodontopathic bacteria. Among tested bacteria, P. gingivalis displayed the greatest sensitivity to macrocarpals; additionally, its trypsin-like proteinase activity and binding to saliva-coated hydroxyapatite beads were inhibited by macrocarpals. These results indicate that eucalyptus leaf extracts may be useful as a potent preventative of periodontal disease.
(キーワード): Anti-Bacterial Agents / Bacterial Adhesion / Bacterial Proteins / Cysteine Endopeptidases / Endopeptidases / Eucalyptus / Plant Extracts / Plant Leaves / Porphyromonas gingivalis / Protease Inhibitors / Sesquiterpenes / Virulence
(出版サイトへのリンク): ● Publication site (DOI): 10.1111/j.1399-302X.2006.00269.x
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 16626372; ● Search Scopus @ Elsevier (PMID): 16626372; ● Search Scopus @ Elsevier (DOI): 10.1111/j.1399-302X.2006.00269.x

(DOI: 10.1111/j.1399-302X.2006.00269.x, PubMed: 16626372) Yutaka Terao, Shigefumi Okamoto, Kosuke Kataoka, Shigeyuki Hamada and Shigetada Kawabata :
Protective immunity against Streptococcus Pyogenes challenge in mice after immunization with fibronectin-binding protein.,
The Journal of Infectious Diseases, Vol.192, No.12, 2081-2091, 2005.

(要約): Surface-associated fibronectin (Fn)-binding proteins of Streptococcus pyogenes play an important role in the bacterial invasion of epithelial cells. We examined the functional domain and protective antigenicity of the Fn-binding protein FbaA. To investigate the functional domain of FbaA and its localization on S. pyogenes, a series of recombinant glutathione S-transferase (GST)-truncated FbaA proteins was used for immunofluorescent microscopy, ligand blotting, and Biacore analyses. Mice were immunized with the truncated proteins for the determination of the immunogenic domains that contribute to protection against S. pyogenes infection. Ligand-blotting and Biacore analyses revealed that the FbaA fragments harboring a proline-rich repeat domain (RD), but not the N- and C-terminal regions, possessed Fn-binding activity. Immunofluorescent microscopy findings showed that the N terminus and RD were exposed to external regions, which suggests that the RD serves as a Fn-binding element on live organisms. Specific antibodies were efficiently induced in N terminus- and RD-immunized mice and demonstrated bactericidal activity against S. pyogenes in vitro. FbaA-immunized mice survived significantly longer than GST-immunized mice after infection with serotype M1 and M49 strains expressing FbaA. The Fn-binding RD and N terminus of FbaA are potential vaccine candidates for M1 strains of S. pyogenes infection.
(キーワード): Adhesins, Bacterial / Animals / Antibodies, Bacterial / Antigens, Surface / Blotting, Far-Western / Disease Models, Animal / Mice / Microscopy, Fluorescence / Protein Binding / Protein Structure, Tertiary / Sequence Deletion / Streptococcal Infections / Streptococcus pyogenes / Survival Analysis
(出版サイトへのリンク): ● Publication site (DOI): 10.1086/498162
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 16288371; ● Search Scopus @ Elsevier (PMID): 16288371; ● Search Scopus @ Elsevier (DOI): 10.1086/498162

(DOI: 10.1086/498162, PubMed: 16288371) Ayako Hino, Satoshi Fukuyama, Kosuke Kataoka, Mi-Na Kweon, Kohtaro Fujihashi and Hiroshi Kiyono :
Nasal IL-12p70 DNA prevents and treats intestinal allergic diarrhea.,
The Journal of Immunology, Vol.174, No.11, 7423-7432, 2005.

(要約): OVA-induced allergic diarrhea occurs as a consequence of over-expression of Th1 inhibitory IL-12p40 monomers and homodimers in the large intestine, establishing a dominant Th2-type environment. In this study, we demonstrate that intranasally administered murine IL-12p70 naked DNA expression plasmids resulted in the synthesis of corresponding cytokine in the large intestinal CD11c(+) dendritic cells, leading to the inhibition of Ag-specific Th2-type response for the prevention of allergic diarrhea and the suppression of clinical symptoms including OVA-specific IgE Ab synthesis. The nasal IL-12p70 DNA treatment proved effective even after the establishment of allergic diarrhea. These results suggest that the mucosal administration of naked IL-12p70 DNA plasmid should be considered as a possible preventive and therapeutic treatment for Th2 cell-mediated food allergic diseases in the intestinal tract.
(キーワード): Administration, Intranasal / Colitis / 細胞質分裂 (cytokinesis) / Diarrhea / Down-Regulation / 遺伝子治療 (gene therapy) / Green Fluorescent Proteins / Immunoglobulin A / Immunoglobulin G / Interleukin-12 / Intestine, Large / Lymphoid Tissue / Nasopharynx / Ovalbumin / Plasmids / Protein Subunits / Spleen / Th2 Cells / Vaccines, DNA
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 15905591; ● Search Scopus @ Elsevier (PMID): 15905591

(PubMed: 15905591) Ryoki Kobayashi, Tomoko Kohda, Kosuke Kataoka, Hideshi Ihara, Shunji Kozaki, David W. Pascual, Herman F. Staats, Hiroshi Kiyono, Jerry R. McGhee and Kohtaro Fujihashi :
A novel neurotoxoid vaccine prevents mucosal botulism.,
The Journal of Immunology, Vol.174, No.4, 2190-2195, 2005.

(要約): The threat posed by botulism, classically a food- and waterborne disease with a high morbidity and mortality, has increased exponentially in an age of bioterrorism. Because botulinum neurotoxin (BoNT) could be easily disseminated by terrorists using an aerosol or could be used to contaminate the food or water supply, the Centers for Disease Control and Prevention and the National Institute of Allergy and Infectious Diseases has classified it as a category A agent. Although clearly the development of a safe and effective mucosal vaccine against this toxin should be a high priority, essentially no studies to date have assessed mucosal immune responses to this disease. To bridge this gap in our knowledge, we immunized mice weekly for 4 wk with nasal doses of BoNT type A toxoid and a mutant of cholera toxin termed E112K. We found elevated levels of BoNT-specific IgG Abs in plasma and of secretory IgA Abs in external secretions (nasal washes, saliva, and fecal extracts). When mice given nasal BoNT vaccine were challenged with 4 x 10(3) LD50 of BoNT type A (BoNT/A) via the i.p. route, complete protection was seen, while naive mice given the same dosage died within 2 h. To further confirm the efficacy of this nasal BoNT vaccine, an oral LD50 was determined. When mice were given an oral challenge of 5 microg (2 x oral LD50) of progenitor BoNT/A, all immunized mice survived beyond 5 days, while nonimmunized mice did not. The fecal extract samples from nasally vaccinated mice were found to contain neutralizing secretory IgA Abs. Taken together, these results show that nasal BoNT/A vaccine effectively prevents mucosal BoNT intoxication.
(キーワード): Adjuvants, Immunologic / Administration, Intranasal / Administration, Oral / Animals / Antibodies, Bacterial / Antibody-Producing Cells / Bacterial Vaccines / Botulinum Toxin Type A / Botulism / Clostridium botulinum type A / Immunity, Innate / Immunoglobulin A, Secretory / Intestinal Mucosa / Mice / Mice, Inbred C57BL / Nasal Mucosa / Toxoids
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 15699151; ● Search Scopus @ Elsevier (PMID): 15699151

(PubMed: 15699151) Naoto Yoshino, Fabien X-S Lü, Kohtaro Fujihashi, Yukari Hagiwara, Kosuke Kataoka, Ding Lu, Linda Hirst, Mitsuo Honda, Frederik Ginkel W. van, Yoshifumi Takeda, Christopher J. Miller, Hiroshi Kiyono and Jerry R. McGhee :
A novel adjuvant for mucosal immunity to HIV-1 gp120 in nonhuman primates.,
The Journal of Immunology, Vol.173, No.11, 6850-6857, 2004.

(要約): The development of a safe and effective mucosal adjuvant is a crucial step toward a mucosal HIV/AIDS vaccine. This study seeks to determine the promise of a nontoxic mutant of cholera toxin (mCT; E112K) as a mucosal adjuvant in nonhuman primates. HIV-1 gp120 was nasally administered together with mCT E112K or native CT (nCT) as adjuvant on five to six occasions over a 6- to 8-wk period to groups of four rhesus macaques and alone to two monkeys that acted as controls. Macaques given nasal gp120 with either mCT E112K or nCT showed elevated gp120-specific IgG and IgA Ab responses with virus-neutralizing activity in both their plasma and mucosal external secretions, as well as higher numbers of gp120-specific IgA Ab-forming cells in their mucosal and peripheral lymphoid tissues and of IL-4-producing Th2-type CD4-positive (CD4(+)) T cells than did controls. Even though significant mucosal adjuvanticity was seen with both mCT E112K and nCT, neuronal damage was observed only in the nCT-treated, but not in the control or mCT E112K-treated groups. These results clearly show that mCT E112K is an effective and safe mucosal adjuvant for the development of a nasal HIV/AIDS vaccine.
(キーワード): AIDS Vaccines / Adjuvants, Immunologic / Animals / Antibody-Producing Cells / Cholera Toxin / Epitopes, T-Lymphocyte / Female / HIV Antibodies / HIV Envelope Protein gp120 / HIV-1 / Immunity, Mucosal / Immunoglobulin A / Immunoglobulin G / Lymphoid Tissue / Macaca mulatta / Male / Nasal Mucosa / Neutralization Tests / Th1 Cells / Th2 Cells
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 15557179; ● Search Scopus @ Elsevier (PMID): 15557179

(PubMed: 15557179) Kazuhiko Maeda, Hideki Nagata, Aya Nonaka, Kosuke Kataoka, Muneo Tanaka and Satoshi Shizukuishi :
Oral streptococcal glyceraldehydes-3-phosphate dehydrogenase mediates interaction with Porphyromonas gingivalis fimbriae.,
Microbes and Infection, Vol.6, No.13, 1163-1170, 2004.

(要約): Interaction of Porphyromonas gingivalis with plaque-forming bacteria is necessary for its colonization in periodontal pockets. Participation of Streptococcus oralis glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and P. gingivalis fimbriae in this interaction has been reported. In this investigation, the contribution of various oral streptococcal GAPDHs to interaction with P. gingivalis fimbriae was examined. Streptococcal cell surface GAPDH activity was measured by incubation of a constant number of streptococci with glyceraldehyde-3-phosphate and analysis for the conversion of NAD+ to NADH based on the absorbance at 340 nm. Coaggregation activity was measured by a turbidimetric assay. Cell surface GAPDH activity was correlated with coaggregation activity (r = 0.854, P < 0.01) with Spearman's rank correlation coefficient. S. oralis ATCC 9811 and ATCC 10557, Streptococcus gordonii G9B, Streptococcus sanguinis ATCC 10556, and Streptococcus parasanguinis ATCC 15909 exhibited high cell surface GAPDH activity and coaggregation activity; consequently, their cell surface GAPDHs were extracted with mutanolysin and purified on a Cibacron Blue Sepharose column. Subsequently, their DNA sequences were elucidated. Purified GAPDHs bound P. gingivalis recombinant fimbrillin by Western blot assay, furthermore, their DNA sequences displayed a high degree of homology with one another. Moreover, S. oralis recombinant GAPDH inhibited coaggregation between P. gingivalis and the aforementioned five streptococcal strains in a dose-dependent manner. These results suggest that GAPDHs of various plaque-forming streptococci may be involved in their attachment to P. gingivalis fimbriae and that they may contribute to P. gingivalis colonization.
(キーワード): Amino Acid Sequence / Bacterial Adhesion / Bacterial Proteins / Blotting, Western / Chromatography, Affinity / DNA, Bacterial / Endopeptidases / Fimbriae, Bacterial / Glyceraldehyde-3-Phosphate Dehydrogenases / Humans / Molecular Sequence Data / NAD / Porphyromonas gingivalis / Protein Binding / Sepharose / Sequence Analysis, DNA / Sequence Homology, Amino Acid / 連鎖球菌 (Streptococcus) / Streptococcus oralis / Streptococcus sanguis
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.micinf.2004.06.005
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 15488735; ● Search Scopus @ Elsevier (PMID): 15488735; ● Search Scopus @ Elsevier (DOI): 10.1016/j.micinf.2004.06.005

(DOI: 10.1016/j.micinf.2004.06.005, PubMed: 15488735) Muneo Tanaka, Yumiko Yamamoto, Masae Kuboniwa, Aya Nonaka, Nobuko Nishida, Kazuhiko Maeda, Kosuke Kataoka, Hideki Nagata and Satoshi Shizukuishi :
Contribution of periodontal pathogens on tongue dorsa analyzed with real-time PCR to oral malodor.,
Microbes and Infection, Vol.6, No.12, 1078-1083, 2004.

(要約): Oral malodor is considered to originate primarily from tongue microbiota populations. However, the relationship between oral malodor and tongue microbiota remains unclear. In this study, tongue periodontal pathogens were analyzed via real-time PCR, and the association between oral malodor and tongue periodontal pathogens, including Porphyromonas gingivalis, Tannerella forsythia, Prevotella intermedia, Prevotella nigrescens and Treponema denticola, was examined. The subject population consisted of 29 individuals with and 10 healthy persons without oral malodor. Oral malodor was assessed by organoleptic test and volatile sulfur compound (VSC) levels as measured by gas chromatography. Real-time PCR was conducted for anaerobes in tongue biofilm samples employing a LightCycler system; furthermore, bacterial proportion served as a quantitative parameter. Among the five anaerobes, only T. forsythia displayed higher proportions in malodor subjects than corresponding values in healthy controls. Proportions of P. intermedia and P. nigrescens correlated strongly with hydrogen sulfide concentration. Proportions of P. gingivalis and P. nigrescens also exhibited strong correlation with methyl mercaptan concentration. The correlation coefficient between the proportion of the total of the five anaerobes and total VSC level (r = 0.88) was greater than that between bacterial proportion and organoleptic score (r = 0.29). When a linear regression analysis was performed utilizing the proportion of each of the five periodontal pathogens as an independent variable, the explanatory power of these independent variables revealed 81% for total VSC level and 16% for organoleptic score. These results suggest that these five periodontal pathogens on tongue dorsa may contribute greatly to VSC production.
(キーワード): Adult / Bacteria, Anaerobic / Bacteroides / Breath Tests / Chromatography, Gas / Female / Halitosis / Humans / Male / Middle Aged / Periodontitis / Polymerase Chain Reaction / Porphyromonas gingivalis / Sulfur Compounds / Tongue / Treponema
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.micinf.2004.05.021
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 15380777; ● Search Scopus @ Elsevier (PMID): 15380777; ● Search Scopus @ Elsevier (DOI): 10.1016/j.micinf.2004.05.021

(DOI: 10.1016/j.micinf.2004.05.021, PubMed: 15380777) Kazuhiko Maeda, Hideki Nagata, Masae Kuboniwa, Kosuke Kataoka, Nobuko Nishida, Muneo Tanaka and Satoshi Shizukuishi :
Characterization of binding of Streptococcus oralis glyceraldehydes-3-phosphate dehydroenase to Porphyromonas gingivalis major fimbriae.,
Infection and Immunity, Vol.72, No.9, 5475-5479, 2004.

(要約): Binding of Streptococcus oralis glyceraldehyde-3-phosphate dehydrogenase (GAPDH) to Porphyromonas gingivalis fimbriae was characterized via a biomolecular interaction analysis system. The interaction was specific, and the association constant value was 4.34 x 10(7) M(-1), suggesting that S. oralis GAPDH functions as a dominant receptor for P. gingivalis and contributes to P. gingivalis colonization.
(キーワード): Biosensing Techniques / Fimbriae Proteins / Fimbriae, Bacterial / Glyceraldehyde-3-Phosphate Dehydrogenases / Humans / Kinetics / Porphyromonas gingivalis / Streptococcus oralis
(出版サイトへのリンク): ● Publication site (DOI): 10.1128/IAI.72.9.5475-5477.2004
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 15322048; ● Search Scopus @ Elsevier (PMID): 15322048; ● Search Scopus @ Elsevier (DOI): 10.1128/IAI.72.9.5475-5477.2004

(DOI: 10.1128/IAI.72.9.5475-5477.2004, PubMed: 15322048) Shinichi Sekine, Kosuke Kataoka, Muneo Tanaka, Hideki Nagata, Toru Kawakami, Kenichi Akaji, Saburo Aimoto and Satoshi Shizukuishi :
Active domains of salivary statherin on apatitic surfaces for binding to Fusobacterium nucleatum cells.,
Microbiology, Vol.150, No.Pt 7, 2373-2379, 2004.

(要約): Fusobacterium nucleatum can bind to saliva-coated tooth surfaces. However, the nature of the domains of salivary protein that interact with F. nucleatum remains unclear. The ability of individual proteins in human submandibular-sublingual saliva (HSMSL) to bind F. nucleatum cells was examined by dot blot assay; statherin displayed the strongest binding activity. Statherin binding sites were determined based on binding of (125)I-labelled F. nucleatum to statherin-coated hydroxyapatite (sHAP) beads via inhibition assays using synthetic analogous peptide fragments of whole statherin. Analogous peptides corresponding to residues 19-26 and 32-39 of statherin inhibited binding by 77 % and 68 %, respectively. Synthetic peptides were also prepared by serial deletions of individual residues from N- and C-termini of the peptides GPYQPVPE (aa 19-26) and QPYQPQYQ (aa 32-39). The inhibitory effects of peptides YQPVPE (aa 21-26) and PYQPQYQ (aa 33-39) were very similar to those of GPYQPVPE and QPYQPQYQ, respectively. However, additional deletion of residues resulted in significant reduction of the inhibitory effect. Alanine-scan analysis of YQPVPE revealed that all tested peptides retained inhibitory activity; only YAPVPE exhibited significantly decreased inhibitory activity. These findings suggest that YQPVPE and PYQPQYQ may represent the minimal active segments of statherin for binding to F. nucleatum; moreover, Gln may be a key amino acid in the active segment.
(キーワード): Amino Acid Sequence / Bacterial Adhesion / Binding Sites / Durapatite / Fusobacterium nucleatum / Humans / Immunoblotting / Molecular Sequence Data / Peptide Fragments / Saliva / Salivary Proteins and Peptides
(出版サイトへのリンク): ● Publication site (DOI): 10.1099/mic.0.27107-0
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 15256578; ● Search Scopus @ Elsevier (PMID): 15256578; ● Search Scopus @ Elsevier (DOI): 10.1099/mic.0.27107-0

(DOI: 10.1099/mic.0.27107-0, PubMed: 15256578) M Tanaka, H Anguri, A Nonaka, Kosuke Kataoka, H Nagata, J Kita and S Shizukuishi :
Clinical assessment of oral malodor by the electronic nose system.,
Journal of Dental Research, Vol.83, No.4, 317-321, 2004.

(要約): A recently developed electronic nose has not yet been clinically applied to evaluations of oral malodor. This investigation sought to determine whether an electronic nose could clinically assess oral malodor. Twenty-nine healthy adults and 49 patients were assessed by results of an actual organoleptic test, a score representing malodor strength with an electronic nose in "top-note" mode (top-note score), and measurements of volatile sulfur compound (VSC) concentrations. The correlation coefficient between top-note and actual organoleptic scores (r = 0.71) was comparable with the log VSC and actual organoleptic scores (r = 0.63). However, the area under the receiver-operating characteristic plots for top-note score was significantly larger than that for log VSC. In logistic regression analyses with top-note score as a dependent variable, probing depth, tongue coating, and plaque control record each had independent associations. Our findings suggest that the top-note score from an electronic nose examination may be useful for the clinical evaluation of oral malodor.
(キーワード): Adult / Biosensing Techniques / Electronics / Evaluation Studies as Topic / Female / Halitosis / Humans / Logistic Models / Male / Middle Aged / Oral Health / Periodontal Index / Sulfur Compounds
(出版サイトへのリンク): ● Publication site (DOI): 10.1177/154405910408300409
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 15044506; ● CiNii @ 国立情報学研究所 (CRID): 1574231875317482752; ● Summary page in Scopus @ Elsevier: 2-s2.0-2342537824

(DOI: 10.1177/154405910408300409, PubMed: 15044506, CiNii: 1574231875317482752, Elsevier: Scopus) Kosuke Kataoka, Jerry R. McGhee, Ryoki Kobayashi, Keiko Fujihashi, Satoshi Shizukuishi and Kohtaro Fujihashi :
Nasal Flt3 ligand cDNA elicits CD11c+CD8+ dendritic cells for enhanced mucosal immunity.,
The Journal of Immunology, Vol.172, No.6, 3612-3619, 2004.

(要約): Nasal immunization is an effective way to induce both mucosal and systemic immune responses. In this study, we assessed a cDNA vector for Flt3 ligand (FL) for its potential to enhance mucosal immunity or tolerance. Interestingly, tolerance was avoided and elevated levels of OVA-specific Ab responses were induced in nasal washes, fecal extracts, and saliva as well as in plasma when compared with mice given nasal OVA plus DNA plasmid without the FL gene. In addition, significant levels of OVA-specific CD4+ T cell proliferative responses and OVA-induced IL-4 and IL-2 production were noted in spleen and cervical lymph nodes. Further, marked increases in FL protein occurred in the nasal lamina propria and submandibular glands and the frequencies of CD11c+CD8+ dendritic cells (DCs) significantly increased in the mucosal tissues. Moreover, these DCs expressed high levels of CD40, CD80, CD86, and MHC class II molecules. Nasal delivery of plasmid FL with OVA resulted in FL expression in both mucosal inductive and effector sites and resulted in expanded activated lymphoid DCs. Thus, nasal plasmid FL prevents mucosal tolerance and enhances active immunity when given by a mucosal route.
(キーワード): Adjuvants, Immunologic / Administration, Intranasal / Animals / Antigens, CD11c / Antigens, CD8 / CD4-Positive T-Lymphocytes / 細胞分裂 (cell division) / 細胞質分裂 (cytokinesis) / DNA, Complementary / Dendritic Cells / Epitopes, T-Lymphocyte / Female / Genetic Vectors / Immunity, Mucosal / Immunoglobulin A / Ligands / Membrane Proteins / Mice / Mice, Inbred C57BL / Nasal Mucosa / Ovalbumin / Vaccines, DNA
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 15004163; ● Search Scopus @ Elsevier (PMID): 15004163

(PubMed: 15004163) Yukari Hagiwara, Jerry R. McGhee, Keiko Fujihashi, Ryoki Kobayashi, Naoto Yoshino, Kosuke Kataoka, Yuri Etani, Mi-Na Kweon, Shinichi Tamura, Takeshi Kurata, Yoshifumi Takeda, Hiroshi Kiyono and Kohtaro Fujihashi :
Protective Mucosal Immunity in Aging Is Associated with Functional CD4+ T Cells in Nasopharyngeal-Associated Lymphoreticular Tissue,
The Journal of Immunology, Vol.170, No.4, 1754-1762, 2003.

(要約): Our previous studies showed that mucosal immunity was impaired in 1-year-old mice that had been orally immunized with OVA and native cholera toxin (nCT) as mucosal adjuvant. In this study, we queried whether similar immune dysregulation was also present in mucosal compartments of mice immunized by the nasal route. Both 1-year-old and young adult mice were immunized weekly with three nasal doses of OVA and nCT or with a nontoxic chimeric enterotoxin (mutant cholera toxin-A E112K/B subunit of native labile toxin) from Brevibacillus choshinensis. Elevated levels of OVA-specific IgG Abs in plasma and secretory IgA Abs in mucosal secretions (nasal washes, saliva, and fecal extracts) were noted in both young adult and 1-year-old mice given nCT or chimeric enterotoxin as mucosal adjuvants. Significant levels of OVA-specific CD4(+) T cell proliferative and OVA-induced Th1- and Th2-type cytokine responses were noted in cervical lymph nodes and spleen of 1-year-old mice. In this regard, CD4(+), CD45RB(+) T cells were detected in greater numbers in the nasopharyngeal-associated lymphoreticular tissues of 1-year-old mice than of young adult mice, but the same did not hold true for Peyer's patches or spleen. One-year-old mice given nasal tetanus toxoid plus the chimeric toxin as adjuvant were protected from lethal challenge with tetanus toxin. This result reinforced our findings that age-associated immune alterations occur first in gut-associated lymphoreticular tissues, and thus nasal delivery of vaccines for nasopharyngeal-associated lymphoreticular tissue-based mucosal immunity offers an attractive possibility to protect the elderly.
(キーワード): Administration, Intranasal / 加齢 (aging) / Animals / Antibody Specificity / Antibody-Producing Cells / CD4-Positive T-Lymphocytes / Cholera Toxin / Cytokines / Immunity, Mucosal / Immunization / Immunoglobulin A / Lymphocyte Activation / Lymphocyte Count / Lymphoid Tissue / Male / Mice / Mice, Inbred BALB C / Mice, Inbred C57BL / Mononuclear Phagocyte System / Nasal Mucosa / Nasopharynx / Ovalbumin / Paralysis / Recombinant Fusion Proteins / T-Lymphocyte Subsets / Tetanus Toxoid
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 12574339; ● Search Scopus @ Elsevier (PMID): 12574339

(PubMed: 12574339) Hirotomo KATO, Kohtaro FIJIHASHI, Rie KATO, Taeko DOHI, Keiko FUJIHASHI, Yukari HAGIWARA, Kosuke Kataoka, Ryoki KOBAYASHI and R. Jerry MCGHEE :
Lack of oral tolerance in aging is due to sequential loss of Peyer's patch cell interactions.,
International Immunology, Vol.15, No.2, 145-158, 2003.

(キーワード): サイトカイン (cytokine) / mucosa / suppression / T h1 / T h2
(出版サイトへのリンク): ● Publication site (DOI): 10.1093/intimm/dxg011
(文献検索サイトへのリンク): ● CiNii @ 国立情報学研究所 (CRID): 1571417124911630592; ● Search Scopus @ Elsevier (DOI): 10.1093/intimm/dxg011

(DOI: 10.1093/intimm/dxg011, CiNii: 1571417124911630592)

MISC

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総説・解説

片岡宏介 :
「口腔感染症および非感染性疾患予防を目指した粘膜ワクチンの開発」-新たな経鼻ダブルDNAアジュバントシステムによる健康長寿社会への貢献-,
日本口腔衛生学会雑誌, Vol.73, No.1, 13-20, 2023年1月.

(徳島大学機関リポジトリ): ● Metadata: 118037

(徳島大学機関リポジトリ: 118037) Kosuke Kataoka :
Development of Mucosal Vaccines as Novel Preventive Methods against Infectious and Noncommunicable Diseases (NCDs): Contribution to a Society of Health and Longevity,
Journal of Oral Health and Biosciences, Vol.35, No.1, 27-32, Sep. 2022.

(要約): The surface layer of the mucosa, which in adult humans, is estimated to have a surface area over 200 times greater than that of the skin, is constantly in contact with foreign antigens, against which non-specific defense (innate immune mechanisms) and specific defense (acquired immune mechanisms) are activated. In the mucosal areas that are the entry points for foreign antigens, the efficient production and secretion of secretory IgA (SIgA) antibodies, which are the main form of specific defense, and mucosal vaccines, which are an efficient antigen delivery system for inducing and promoting antibody production, may offer a strategic tool for preventing not only infections, but also the development of lifestyle-related diseases. We have previously undertaken research and development of an immunostimulating agent (adjuvant) for use with mucosal vaccines based on mucosal immunity, particularly nasal vaccines that are administered to the nasal cavity. More specifically, a double DNA adjuvant (dDA) system that targets dendritic cells, which are one of antigen-presenting cells, was developed, and basic research was conducted using a number of different antigens, including a comparison of the immune response to these antigens when they were introduced into the nasal cavities of young and old experimental animals (mice). Of late, we have been working toward the development of a mucosal vaccine capable of preventing infection or lifestyle-related disease that can also be used in older people. In this review article, I will introduce the advantages of mucosal vaccines as well as recent findings in our group.
(キーワード): Nasal vaccine / DNA Adjuvant / double DNA adjuvant (dDA) / Dendritic cells / Prevention of infectious and noncommunicable diseases
(徳島大学機関リポジトリ): ● Metadata: 117504
(出版サイトへのリンク): ● Publication site (DOI): 10.20738/johb.35.1_27
(文献検索サイトへのリンク): ● CiNii @ 国立情報学研究所 (CRID): 1050293633442984320; ● Search Scopus @ Elsevier (DOI): 10.20738/johb.35.1_27

(徳島大学機関リポジトリ: 117504, DOI: 10.20738/johb.35.1_27, CiNii: 1050293633442984320) 片岡宏介 :
ダブルDNAアジュバントシステムによる唾液分泌型IgA抗体誘導と抗免疫老化,
神奈川歯学, Vol.56, No.2, 141-143, 2021年10月.

(徳島大学機関リポジトリ): ● Metadata: 117503
(文献検索サイトへのリンク): ● CiNii @ 国立情報学研究所 (CRID): 1390011575627053824

(徳島大学機関リポジトリ: 117503, CiNii: 1390011575627053824) 片岡宏介 :
アルカリ性の飲み物を頻回に飲めば，う蝕のリスクは高まらない?,
歯科衛生士, Vol.45, No.6, 23, 2021年6月.

(キーワード): う蝕予防 / アルカリ性

Kosuke Kataoka, Yoshiko Fukuyama, E D Briles, T Miyake and K Fujihashi :
Dendritic cell-targeting DNA-based nasal adjuvants for protective mucosal immunity to Streptococcus pneumoniae.,
Microbiology and Immunology, Vol.61, No.6, 195-205, Sep. 2017.

(要約): To develop safe vaccines for inducing mucosal immunity to major pulmonary bacterial infections, appropriate vaccine antigens (Ags), delivery systems and nontoxic molecular adjuvants must be considered. Such vaccine constructs can induce Ag-specific immune responses that protect against mucosal infections. In particular, it has been shown that simply mixing the adjuvant with the bacterial Ag is a relatively easy means of constructing adjuvant-based mucosal vaccine preparations; the resulting vaccines can elicit protective immunity. DNA-based nasal adjuvants targeting mucosal DCs have been studied in order to induce Ag-specific mucosal and systemic immune responses that provide essential protection against microbial pathogens that invade mucosal surfaces. In this review, initially a plasmid encoding the cDNA of Flt3 ligand (pFL), a molecule that is a growth factor for DCs, as an effective adjuvant for mucosal immunity to pneumococcal infections, is introduced. Next, the potential of adding unmethylated CpG oligodeoxynucleotide and pFL together with a pneumococcal Ag to induce protection from pneumococcal infections is discussed. Pneumococcal surface protein A has been used as vaccine for restoring mucosal immunity in older persons. Further, our nasal pFL adjuvant system with phosphorylcholine-keyhole limpet hemocyanin (PC-KLH) has also been used in pneumococcal vaccine development to induce complete protection from nasal carriage by Streptococcus pneumoniae. Finally, the possibility that anti-PC antibodies induced by nasal delivery of pFL plus PC-KLH may play a protective role in prevention of atherogenesis and thus block subsequent development of cardiovascular disease is discussed.
(キーワード): Adjuvants, Immunologic / Administration, Intranasal / Animals / Antibodies, Bacterial / Antigens, Bacterial / Bacterial Proteins / DNA, Complementary / Dendritic Cells / Hemocyanins / Humans / Immunity, Mucosal / Membrane Proteins / Oligodeoxyribonucleotides / Phosphorylcholine / Pneumococcal Infections / Pneumococcal Vaccines / Streptococcus pneumoniae / Vaccines, DNA
(徳島大学機関リポジトリ): ● Metadata: 117498
(出版サイトへのリンク): ● Publication site (DOI): 10.1111/1348-0421.12487
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 28463465; ● Summary page in Scopus @ Elsevier: 2-s2.0-85020653025

(徳島大学機関リポジトリ: 117498, DOI: 10.1111/1348-0421.12487, PubMed: 28463465, Elsevier: Scopus) 片岡宏介, 土居貴士, 神光一郎, 上根昌子, 伊藤博夫, 落合(栗田) 智子, 三宅達郎 :
樹状細胞を活性化する経鼻アジュバントの開発-感染症・NCD制御を目指す粘膜ワクチン-,
口腔衛生学会雑誌, Vol.67, No.2, 2-10, 2017年6月.

(キーワード): 樹状細胞 (dendritic cell) / 経鼻アジュバント / 粘膜ワクチン / 感染症・NCDs
(徳島大学機関リポジトリ): ● Metadata: 117497
(出版サイトへのリンク): ● Publication site (DOI): 10.5834/jdh.67.1_2
(文献検索サイトへのリンク): ● Search Scopus @ Elsevier (DOI): 10.5834/jdh.67.1_2

(徳島大学機関リポジトリ: 117497, DOI: 10.5834/jdh.67.1_2) 木戸博, 高橋悦久, 片岡宏介, 水野大, 木本貴司, 藤本知佐, Indarao L. Irene :
インフルエンザ感染症における粘膜免疫とその制御による治療効果の増強,
新薬と臨床, Vol.61, No.12, 2459-2470, 2012年12月. 木戸博, 高橋悦久, 片岡宏介, 水野大, 木本貴士, 藤本知佐, Indalao L Irene :
インフルエンザ感染症における粘膜免疫とその制御による治療効果の増強,
新薬と臨床, Vol.61, No.12, 2459-2470, 2012年12月. 木戸博, 高橋悦久, 片岡宏介, 矢野仁康, 鈴木悟 :
気道の生体防御能，粘膜免疫を増強するマクロライド系薬とインフルエンザ感染,
医薬ジャーナル, Vol.47, No.11, 2768-2733, 2011年11月. 雫石聰, 田中宗雄, 小島美樹, 西田伸子, 永田英樹, 片岡宏介, 久保庭雅恵 :
第2章「歯周病と喫煙との関連性についてのEBM」,
生命歯科医学のカッティング・エッジ Cutting-Edge Biodentistry, 109-119, 2008年3月.

講演・発表

Kayo Koyanagi, Kosuke Kataoka, Shizuko Yanagisawa and Tatsuro Miyake :
Involvement of human salivary protein-derived peptides-specific 1 SIgA in oral P.2 gingivalis colonization,
Japan Association for Dental Research (JADR 2021), Oct. 2021. Kosuke Kataoka, Keita Oma, Yoshiko Fukuyama, K. Susan Hollingshead, Shinichi Sekine, Shigetaka Kawabata, E. David Briles, Kazunori Oishi and Kohtaro Fujihashi :
Nasal dendritic cell targeting Flt3 ligand as a safe adjuvant elicits effective protection against fatal pneumococcal pneumonia.,
15th International Congress of Mucosal Immunology, Paris, Jul. 2011. S. A. Mulyatno, M. Fukui, M. Mani, K. Uno, Kosuke Kataoka and H.-O. Ito :
Cytokine profile in human saliva and its relationship with that in blood.,
International Joint QOL Symposium on Oral Science, Bali, Indonesia, Dec. 2010. Makoto Fukui, M. Mani, K. Uno, Kosuke Kataoka and Hiro-O Ito :
Cytokine profile in human saliva and its relationship with that in blood.,
9th International Conference Asian Academy of Preventive Dentistry, Kuala Lumpur, Malaysia, Nov. 2010. Hiroshi Kido, Etsuhisa Takahashi, Kosuke Kataoka, K. Fujii, S. Suzuki and C. Ito :
Attenuation of Respiratory Immune Responses by Antiviral Neuraminidase Inhibitor Treatment and Boost of Mucosal Immunoglobulin A Response by Coadministration of Immunomodulator Clarithromycin in Pediatric Imfluenza,
Options fot the Control of Influenza, Hong Kong SAR, China, Sep. 2010. Kosuke Kataoka, Ke. Fujihashi, R. Kobayashi, S. R. Gilbert, S. Sekine, Makoto Fukui, Y. Fukuyama, S. Kawabata, Hiro-O Ito and Ko. Fujihashi :
Nasal Cholera Toxin Activated Mucosal Densritic Cells, but not CD4+ Cells Elicits TI-IgA Class Switching Recombination by B-1 B Cells.,
14th International Congress of Immunology, Aug. 2010. T. Baatarjav, Kosuke Kataoka, Makoto Fukui, A. S. Mulyatno, K. Fujihashi and Hiro-O Ito :
Nasal Vaccination with Phosphorylcholine plus Flt3 Ligand Gene as a Mucosal Adjuvant Inhibits Streptococcus pneumoniae Colonization.,
14th International Congress of Immunology, Kobe, Aug. 2010. Sinichi Sekine, Ryoki kobayashi, Mika Sasaki, Yoshiko Fukuyama, N. Asanuma, S. R. Gilbert, Ke. Fujihashi, Kosuke Kataoka and Ko. Fujihashi :
Characterization of Mucosal Immunosenescence in Nasopharyngeal-Associated Lymphoreticular Tissue.,
14th International Congress of Immunology, Kobe, Aug. 2010. Dara S.Arini, 一ノ宮美咲, 片岡宏介, 松香芳三 :
ラット三叉神経痛モデルにおけるクルクミン全身投与効果,
近畿・中国・四国口腔衛生学会, 2024年9月. 高橋悦久, 片岡宏介, Indalao Lorinda Irene, 木戸博 :
インフルエンザ感染時のタミフル服用により低下した気道粘膜IgAはクラリスロマイシンと併用することによって改善される,
第54回日本生化学会中国四国支部例会, 2013年5月. 木葉敬子, 高橋悦久, 片岡宏介, Indalao Lorinda Irene, 木戸博 :
Airway mucosal IgA which reduced by oseltamivir is improved by combination with Clarithromycin in mice infected with influenza A virus,
第85回日本生化学会大会, 2012年12月. 天羽崇, 日野出大輔, 平島美穂, 吉岡昌美, 横山正明, 玉谷香奈子, 福井誠, 伊藤博夫, 片岡宏介 :
舌苔中の歯周病関連細菌と口臭との関連性,
第23回近畿中国四国口腔衛生学会総会, 2012年10月. SA Mulyatno, Kosuke Kataoka, Makoto Fukui, Kaname Miki, RC Orihuela-Campos and Hiro-O Ito :
Modulation of Mucosal Immune Response by Bacterial Lipopolysaccharide in Nasal Vaccination Model,
第61回日本口腔衛生学会・総会, May 2012. 福井誠, SA Mulyatno, 後藤優樹, 三木かなめ, RC Orihuela-Campos, 片岡宏介, 林田秀明, 北村雅保, 川崎浩二, 関田孝晴, 中里未央, 前田隆浩, 齋藤俊行, 伊藤博夫 :
ヒト唾液中および血中の抗ホスホリルコリン抗体と動脈硬化リスクとの関連性-第二報-,
第61回日本口腔衛生学会・総会, 2012年5月. 福井誠, ムルヤトノサプタ, バータルジャフツェルメグ, 後藤優樹, 片岡宏介, 林田秀明, 川崎浩二, 前田隆浩, 中里未央, 齋藤俊行, 伊藤博夫 :
ヒト唾液中および血中の抗ホスホリルコリン抗体と動脈硬化リスクとの関連性:五島研究,
2011年10月. ムルヤトノサプタ, 片岡宏介, 関根伸一, バータルジャブツェルメグ, 福井誠, 金川裕子, 後藤優樹, 伊藤博夫 :
経鼻粘膜アジュバントCpG ODNはマクロファージのTLR9発現と歯周病細菌抗原特異的Th1免疫応答を誘導する,
2011年10月. 渋谷敦人, 小林弘茂, 福井隆夫, 岡田寿朗, 豊嶋健治, 福井誠, 片岡宏介, 伊藤博夫, 奥弘文 :
平成22年度に香川県内で実施された成人歯科健診モデル事業実施報告,
2011年10月. 武川香織, 真杉幸江, 十川悠香, 坂本治美, 福井誠, 片岡宏介, 吉岡昌美, 日野出大輔 :
妊婦歯科健康診査受診者の妊娠中の歯周状態と出産の状況について,
第22回近畿・中国・四国口腔衛生学会総会抄録集, 19, 2011年10月. 片岡宏介 :
受動免疫型および能動免疫型ワクチン開発への挑戦~粘膜免疫学と分子生物学を基盤とした予防歯科学的展開~,
第59回口腔衛生学会総会シンポジウム「口腔の健康を科学する」, 2010年10月. T. Baatarjav, Kosuke Kataoka, S. Mulyatno, Makoto Fukui, H. Kanagawa and Hiro-O Ito :
Nasal Flt3L gene results in mucosal immune responses to PC through induction of B-1 B cells.,
第59回口腔衛生学会総会, Oct. 2010. 片岡宏介, 関根伸一, バータルジャフツェルメグ, ムルヤトノサプタ, 福井誠, 金川裕子, 伊藤博夫 :
遺伝子改変植物による歯周病原菌定着阻害能を有するヒト唾液タンパク質スタセリンペプチドの発現,
第59回口腔衛生学会総会, 2010年10月. 関根伸一, 片岡宏介, 東江正裕, 橋野恵衣, 岩崎未央, 田中宗雄, 新庄文明 :
佐用町台風第9号災害における住民の口腔保健調査,
第59回口腔衛生学会総会, 2010年10月. 福井誠, ムルヤトノサプタ, バータルジャフツェルメグ, 片岡宏介, 林田秀明, 川崎浩二, 斎藤俊行, 伊藤博夫 :
ヒト血中および唾液中の抗ホスホリルコリン抗体の存在実態,
第59回口腔衛生学会総会, 2010年10月. 関根伸一, 片岡宏介, 岩崎未央, 橋野恵子, 東江正裕 :
Flt3 ligand cDNA 及びCpG ODNは粘膜アジュバントとしてP. gingivalis抗原特異的抗体反応を誘導する,
第53回日本歯周病学会秋季学術大会, 2010年9月. 片岡宏介, 関根伸一, 福井誠, 横山正明, 伊藤博夫 :
粘膜アジュバントCpG オリゴヌクレオチドによるPorphyromonas gingivalis 線毛抗原特異的抗体応答の誘導,
第53回日本歯周病学会秋季学術大会, 2010年9月. 片岡宏介, 福井誠, 金川裕子, 伊藤博夫 :
ヒト唾液タンパク質由来ペプチドの歯周病菌定着阻害効果,
第21回近畿・中国・四国口腔衛生学会総会, 2010年6月. 福井誠, サプタムルヤトノ, バータルジャフツェルメグ, 片岡宏介, 伊藤博夫 :
ヒトの唾液中および血中に存在する抗ホスホリルコリン抗体の検出,
第21回近畿・中国・四国口腔衛生学会総会, 2010年6月. 三崎昌和, 渋谷敦人, 岡田寿朗, 阿部直樹, 豊嶋健治, 福井誠, 片岡宏介, 伊藤博夫, 奥弘文 :
平成21年度に香川県内で実施された成人歯科健診モデル事業実施報告,
第21回近畿・中国・四国口腔衛生学会総会, 2010年6月. 片岡宏介, 中垣晴男, 関根伸一, 福井誠, 伊藤博夫, 雫石聰 :
Fusobacterium nucleatum表層タンパク質FomAと唾液高チロシンタンパク質スタセリンペプチドとの相互作用,
第53回日本歯周病学会春季学術大会, 2010年5月. 片岡宏介 :
粘膜免疫と粘膜免疫システムを応用した樹状細胞誘導型経鼻アジュバントの開発,
2010年2月. Kosuke Kataoka, Hiro-O Ito, Makoto Fukui, Baatarjav Tselmeg and 藤橋浩太郎 :
Induction of PC-specific T15 idiotype Ab in mucosal secretion by Flt3 ligand plasmid as a mucosal adjuvant,
日本免疫学会総会学術集会記録, Vol.39, 193, Dec. 2009. バータルジャフツェルメグ, ムルヤトノサプタ, 金川裕子, 片岡宏介, 伊藤博夫, 福井誠 :
唾液タンパク質由来ペプチド複合体による歯周病菌定着阻害能の検討,
第59回日本口腔衛生学会総会(岐阜市，長良川国際会議場) 口腔衛生学会雑誌, Vol.59, No.4, 349, 2009年10月. 福井誠, 日野出大輔, 横山正明, バータルジャフツェルメグ, 片岡宏介, 伊藤博夫 :
フゾバクテリウム反応性唾液sIgA抗体と舌苔との関連性,
口腔衛生学会雑誌, Vol.59, No.5, 606-607, 2009年6月.

(キーワード): *Secretory IgA

伊藤博夫, B. ツェルメグ, 片岡宏介, 福井誠 :
肺炎球菌抗原とDNAアジュバント経鼻投与による粘膜免疫応答の解析,
第20回日本口腔衛生学会近畿·中国·四国地方会 (広島国際会議場), 2009年6月.

研究会・報告書: 研究者総覧に該当データはありませんでした。

特許: 片岡宏介, 久保庭雅恵, 堀江博, 永田秀樹, 天野敦雄, 雫石聰 : 特願9-286229 (1997年), 特開11116453 (1999年), .
作品: 研究者総覧に該当データはありませんでした。
補助金・競争的資金: NALT樹状細胞標的型粘膜アジュバントの免疫老化レジリエンス機序解明のための基盤構築 (研究課題/領域番号: 24K02659 )
高齢者気道組織を再現する動物モデルを用いた肺炎発症機構の解明と診断法への応用 (研究課題/領域番号: 23K24559 )
舌下免疫で誘導される制御性T細胞の組織間移動によるI型アレルギー抑制機序の解明 (研究課題/領域番号: 22K10327 )
蛍光イメージングによる唾液IgA抗体産生に関わる免疫細胞生体内ダイナミクスの解明 (研究課題/領域番号: 20H03902 )
舌下ワクチンによる老化粘膜免疫回復：歯周病と動脈硬化の予防と治療 (研究課題/領域番号: 20H03856 )
新規粘膜アジュバントを用いた経鼻ワクチンによる動脈硬化アテローム形成抑制能の検証 (研究課題/領域番号: 19K10474 )
舌下粘膜組織に存在する免疫細胞クラスターの口腔免疫応答における役割の解明 (研究課題/領域番号: 18K09930 )
ストレス誘導性老化細胞の挙動解析から迫る未知なる骨形成阻害機構の解明 (研究課題/領域番号: 18H02986 )
唾液タンパク由来ペプチド抗原に対する分泌型IgA抗体の歯周病細菌付着阻害能の検証 (研究課題/領域番号: 17K12034 )
唾液腺におけるIgA抗体形質細胞への最終分化メカニズムの解明と加齢が及ぼす影響 (研究課題/領域番号: 17H04424 )
ビスフォスフォネート関連顎骨壊死発症・進行における歯周病菌の口腔免疫学的影響 (研究課題/領域番号: 22659383 )
細菌やヒト細胞に存在する多機能タンパク質GAPDHが歯周病細菌感染に果たす役割 (研究課題/領域番号: 20390534 )
胸腺非依存性抗原特異的唾液IgA抗体誘導のための自然免疫賦活化メカニズムの解明 (研究課題/領域番号: 19592403 )
歯周病がメタボリックシンドロームの病態に及ぼす分子メカニズムの解明 (研究課題/領域番号: 19209064 )
金属結合ヒト唾液タンパク質の経口投与による金属アレルギー発症動物モデルの作製 (研究課題/領域番号: 18659628 )
歯周病原性菌と口腔レンサ球菌とのバイオフイルム形成に関与する遺伝子群の包括的探索 (研究課題/領域番号: 18592276 )
デザインペプチドライブラリー構築による細菌付着阻止分子探索と感染性心内膜炎予防 (研究課題/領域番号: 18390569 )
ヒト細胞への歯周病細菌の付着、侵入およびシグナル伝達に関する分子メカニズムの解明 (研究課題/領域番号: 18390567 )
T細胞非依存性抗原特異的唾液IgA産生における経鼻アジュバントの機能解明 (研究課題/領域番号: 17592179 )
歯周病細菌の菌体間結合分子メカニズムの解明とバイオフィルム阻害剤の開発 (研究課題/領域番号: 17390564 )
老人性肺炎に関与する口腔細菌の定着を阻害するペプチドの開発 (研究課題/領域番号: 13672145 )
歯周病原性菌の定着を促す唾液タンパク質遺伝子を導入した歯周病惹起動物モデルの作製 (研究課題/領域番号: 11771315 )
歯周病原性菌の鉄獲得機構とその病原性に関する分子生物学的解析 (研究課題/領域番号: 11307050 )
歯周病原性菌のペリクルへの付着を阻害するペプチドの連鎖球菌への遺伝子導入と発現 (研究課題/領域番号: 09771829 )
デンタルプラークへの歯周病原性菌の定着を阻害するペプチドの開発 (研究課題/領域番号: 09557175 )
ポルフィロモナスジンジバリスのヘモグロビン結合性蛋白質の精製と遺伝子クローニング (研究課題/領域番号: 08672155 )
唾液タンパク質の歯周病原性細菌に対するレセプター領域の構造と機能の解析 (研究課題/領域番号: 08457568 )
歯肉微小循環動態からみた喫煙による歯周組織の破壊機序 (研究課題/領域番号: 07457506 )
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2024年11月14日更新

専門分野・研究分野: 予防歯科学 (Preventive Dentistry)
口腔衛生学 (Oral Health)
粘膜免疫
所属学会・所属協会: 日本口腔衛生学会
日本免疫学会
The American Association of Immunologists
国際歯科研究学会
日本歯周病学会
国際粘膜免疫学会
大阪大学歯学会
四国歯学会
近畿・中国・四国口腔衛生学会
日本生化学会
日本唾液ケア研究会
委員歴・役員歴: 日本口腔衛生学会 (代議員 [1999年4月〜2025年4月], 編集委員会副委員長 [2017年4月〜2025年4月], 指導医認定委員会委員 [2021年4月〜2025年4月], 利益相反委員会委員 [2021年4月〜2025年4月])
四国歯学会 (評議員 [2008年4月〜2023年3月])
近畿・中国・四国口腔衛生学会 (常任幹事 [2008年4月〜2024年3月])
日本生化学会 ( [2009年5月〜2012年5月])
日本口腔衛生学会 (代議員,編集委員会委員,利益相反委員会委員,認定制度運営委員会委員 [1993年4月〜2025年3月])
日本口腔衛生学会 (編集委員 [2017年5月〜2023年5月])
日本唾液ケア研究会 (理事・評議員 [2023年4月〜2025年3月])
受賞: 2001年4月, (大阪大学)
2005年6月, Young Investigator Award (International Congress of Mucosal Immunology)
2007年10月, 学術賞 (日本口腔衛生学会)
2011年7月, 学部長表彰優秀教育賞 (徳島大学歯学部)
2017年8月, 第33回「歯科医学を中心とした総合的な研究を推進する集い」 (日本歯科医学会)
2021年2月, グッドティーチャー賞 (大阪歯科大学)
2022年2月, 康楽賞 (公益財団法人康楽会)
活動: 独立行政法人日本学術振興会科学研究費委員会 (専門委員 [2009年11月〜2011年11月])
( [2022年4月〜2023年3月])
大阪大谷大学市民公開講座 ( [2021年10月])
徳島県歯科医師会 ( [2023年11月])
社団法人徳島県医師会 ( [2024年3月〜3月])
学部内学生委員会副委員長 (2021年4月〜2025年3月)
FD委員会委員 (2021年4月〜2025年3月)
高等教育研究センター委員 (2021年4月〜2025年3月)
学部学生国際相互交流担当実施委員会委員 (2021年4月〜2025年3月)
大学院口腔科学研究科教育教育プログラム評価委員会委員 (2021年4月〜2025年3月)
教務委員会委員 (2023年4月〜2025年3月)
企画調整委員会委員 (2023年4月〜2025年3月)
病院運営会議委員 (2024年4月〜)

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2024年11月10日更新

2024年11月9日更新

Ｊグローバル

Jグローバル最終確認日: 2024/11/9 01:36
氏名（漢字）: 片岡宏介
氏名（フリガナ）: カタオカコウスケ
氏名（英字）: Kataoka Kosuke
所属機関: 徳島大学教授
大阪歯科大学
昭和大学

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researchmap最終確認日: 2024/11/10 03:43
氏名（漢字）: 片岡宏介
氏名（フリガナ）: カタオカコウスケ
氏名（英字）: Kataoka Kosuke
プロフィール: リサーチマップAPIで取得できませんでした。
登録日時: 2009/5/11 00:00
更新日時: 2024/8/24 10:57
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所属ID: 0344023000
所属: 徳島大学
部署: 大学院口腔科学教育部
職名: 教授
学位: 歯学博士
学位授与機関: 大阪大学
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ＫＡＫＥＮで最新データを確認する

2024年11月9日更新

研究者番号: 50283792

所属（現在）: 2024/4/1 : 徳島大学, 大学院医歯薬学研究部(歯学域), 教授

所属（過去の研究課題 情報に基づく）*注記: 2020/4/1 – 2024/4/1 : 徳島大学, 大学院医歯薬学研究部(歯学域), 教授
2017/4/1 – 2021/4/1 : 大阪歯科大学, 歯学部, 准教授
2020/4/1 : 徳島大学, 歯学部, 教授
2012/4/1 : 徳島大学, ヘルスバイオサイエンス研究部, 准教授
2010/4/1 – 2011/4/1 : 徳島大学, 大学院・ヘルスバイオサイエンス研究部, 准教授
2008/4/1 : 徳島大学, 大学院・ヘルスバイオサイエンス研究部, 准教授
2007/4/1 : 大阪大学, 大学院・歯学研究科, 助教
2007/4/1 : 大阪大学, 歯学研究科, 助教
2006/4/1 : 大阪大学, 大学院歯学研究科, 助手
2006/4/1 : 大阪大学, 歯学研究科, 助手
2005/4/1 : 大阪大学, 大学院・歯学研究科, 助手
2000/4/1 – 2001/4/1 : 大阪大学, 大学院・歯学研究科, 助手
1996/4/1 – 1999/4/1 : 大阪大学, 歯学部, 助手

審査区分/研究分野

研究代表者

医学 / 歯学 / 矯正・小児・社会系歯学
生物系 / 医歯薬学 / 歯学 / 社会系歯学
小区分57080:社会系歯学関連

研究代表者以外

医学 / 歯学 / 病態科学系歯学(含放射線系歯学)
生物系 / 医歯薬学 / 歯学 / 社会系歯学
医学 / 歯学 / 矯正・小児・社会系歯学
小区分57080:社会系歯学関連
小区分57040:口腔再生医学および歯科医用工学関連
小区分57020:病態系口腔科学関連

キーワード

研究代表者

歯周病原性菌 / Porphyromonas gingivalis / プロリンリッチプロテイン / 線毛 / 初期付着 / 形質転換 / 共凝集 / シャトルプラスミドベクター / 形質転移 / 唾液タンパク質 / proline-rich protein / 発現プラスミドベクター / transfection / 予防歯学 / ワクチン / アジュバント / 粘膜免疫 / 自然免疫 / 唾液IgA抗体 / 経鼻免疫 / クラススイッチング / T細胞非依存性抗原 / 樹状細胞 / B細胞 / IL-5 / 唾液IgA / ビスフォスフォネート / 歯周病菌 / 顎骨壊死 / 骨免疫 / 破骨細胞 / サイトカイン / 顎骨壤死 / 歯周病 / 予防ワクチン / 分泌型IgA抗体 / 定着阻害 / 唾液 / スタセリン / Fusobacteium nucleatum / 結合領域 / Fusobacterium nucleatum / 結合部位 / statherin / F. nucleatum / bindingsite / 粘膜アジュバント / BIB細胞 / B1B細胞 / mucosal immunity / nasal immunization / salivary IgA / nasal adjuvant / Bl B cells / innate immunity / T cell independent antigen / 分泌型IgA (SIgA) / 唾液腺 / 鼻咽腔関連リンパ組織(NALT) / IgA抗体産生細胞 / 形質細胞 / T細胞 / 唾液分泌型IgA抗体 / 唾液腺IgA抗体 / IgA形質細胞 / マウス唾液腺 / 最終分化 / CD４陽性T細胞 / 分化 / 顎下唾液腺 / 老化 / 経鼻ワクチン / 経鼻投与 / 遺伝子改変マウス / マウス舌下唾液腺 / NALT / IgAクラススイッチング / KikGRマウス / Iμ-Cα transcripts / CD11c-YFPマウス / AID / 抗免疫老化 / マウス

研究代表者以外

歯周病原性菌 / P.gingivalis / ヘモグロビン結合性タンパク質 / タンパク分解酵素 / リコンビナントタンパク質 / 鉄源 / 発現誘導 / 予防歯科学 / 感染症 / ペプチド / ライブラリー / 定着抑制 / 口腔細菌 / fibronectin / phosphoiylchaline / レンサ球菌 / ペプチドライブラリー / フィブロネクチン / phosphorylcholine / スクリーニング / バイオアッセイ / オンビーズライブラリー / オンビースライブラリー / 感染性心内膜炎 / 金属アレルギー / IV型アレルギー / 唾液タンパク質 / ニッケル / 動物モデル / メタボリックシンドローム / 歯周病 / 疫学 / 分子生物学 / 歯周病原性細菌歯肉上皮細胞 / バイオフィルム / Porphyromonas gingivalis / Fusobacterium nucleatum / 免疫 / 糖尿病 / 血清脂質異常 / 炎症性サイトカイン / 動脈硬化性疾患 / 歯周病細菌 / 肥満 / 血圧高値 / 空腹時血糖 / 循環器疾患 / バイオマーカー / GAPDH / ヒト細胞 / 感染 / 付着 / 喫煙 / 血流量 / 酸素分圧 / ニコチン / 歯肉 / 歯周ポケット / レーザードップラー / Cigarette smoking / Blood flow / Oxygen tension / Nicotine / Gingival tissue / Periodontal pocket / Laser Doppler flowmeter / 線毛 / prolone-rich protein / statherin / proline-rich glycoprotein / 結合 / proline-rich protein / エピトープマッピング / periodontopathogen / fimbriae / salivary protein / binding / 共凝集 / Streptococcus oralis / periodontopathic bacteria / coaggregation / Actinobacillus actinomycetemcomitans / Prevotella / 鉄 / ヘモグロビン / ビルレンス因子 / ヘモグロビン結合タンパク質 / Actionbacillus actinomycetemcomitans / Prevotella nigrescens / ヘモグロビン結合蛋白質 / 制御因子 / 代謝 / Iron / hemoglobin / Virulence factor / hemoglobin-binding protein / 菌体間相互作用 / interaction among bacteria / biofilm / ヒト歯肉線維芽細胞 / 侵入 / ヒト線維芽細胞 / human gingival fibroblast / fimhriae / adherence / invasion / Streptococcus gordonii / バイオフイルム / 菌体間シグナル / 菌体内シグナル / 莢膜 / 細胞壁 / クオラムセンシング / Porphyromones gingivalis / inter cellular signaling / intra cellular signaling / capsule / cell wall / quorum sensing / ヒト唾液タンパク / DNA粘膜アジュバント / 経鼻ワクチン / 唾液分泌型IgA抗体 / 初期付着阻害 / 唾液IgA抗体誘導 / 唾液腺 / IgA抗体 / 唾液 / 唾液タンパク / 分泌型IgA抗体 / 付着阻害 / 口腔粘膜免疫 / 樹状細胞 / クラスター / 舌下免疫 / 口腔免疫応答 / 免疫細胞クラスター / 老化細胞 / 老化 / 細胞老化 / 骨 / 再生 / 生体材料 / ストレス誘導性老化 / 骨再生 / 骨形成 / カテキン / ストレス / 再生医療 / ホスホリルコリン / 粘膜アジュバント / アテローム沈着抑制 / B-1a B細胞 / APRIL/BAFF分子 / TACI分子 / T15 idiotype / アテローム性動脈硬化 / 経鼻ワクチンアジュバント / APRIL / BAFF / TACI / 動脈硬化 / 経鼻投与 / DNAワクチン / 抗体 / アテローム形成 / 舌下ワクチン / 高原特異的IgA / サイトカイン / 歯槽骨吸収 / 抗原特異的IgA / 粘膜ワクチン / 粘膜免疫 / 分泌型IgA / 唾液IgA抗体 / アジュバント / I型アレルギー反応 / 皮膚感作 / 長期生存型IgE産生細胞 / 舌下免疫療法 / IgE陽性Ｂ細胞 / 制御性Ｔ細胞 / 細菌性肺炎 / インフルエンザ / 肺炎 / 高齢者気道組織

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片岡 宏介

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片岡宏介