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細菌感染によるオートファジー誘導の分子機構の解明

Research Project

Project/Area Number 18050018
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionOsaka University

Principal Investigator

天野 敦雄  Osaka University, 大学院・歯学研究科, 教授 (50193024)

Co-Investigator(Kenkyū-buntansha) 中川 一路  東京大学, 医科学研究所, 准教授 (70294113)
稲葉 裕明  大阪大学, 大学院歯学研究科, 助手 (70359850)
Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥6,600,000 (Direct Cost: ¥6,600,000)
Fiscal Year 2007: ¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2006: ¥3,300,000 (Direct Cost: ¥3,300,000)
Keywords歯学 / 細菌 / 感染症 / 細胞・組織 / シグナル伝達 / オートファジー / A群レンサ球菌 / 細胞内侵入細菌 / 自然免疫システム / Nod-like receptor
Research Abstract

歯周病細菌の宿主細胞内侵入経路および、細胞内侵入後の同菌の細胞内動態につき検討を加えた。オートファジーが細胞内に侵入した細菌を駆逐する分子メカニズムについても検討を加えた。その結果、下記3つの知見が得られた。
1.歯周病細菌P.gingivalisの細胞侵入に関与する宿主因子は、リピッドラフト、α5β1インテグリン、small-GTPaseのRacl、アクチン、微小管の他、アクチンの再構築やエシドサイトーシスに関わる分子であった。
2.エンドサイトーシス経路を利用して細胞内に侵入した歯周病紬菌は、一部は後期エンドソームに包まれたまま分解されてしまうが、一部は初期エンドソームから脱出し、細胞質内に留まる菌と、オートファジーによって殺される菌とがあることが示された。このオートファジー誘導のメカニズムについては明確な結果が得られなかった。今後の研究課題である。
3.歯周病細菌の細胞侵入に不可央な線毛には6つの遺伝子多型が存在し、II型線毛遺伝子をもつ菌株は効率よく歯周細胞に侵入し、強力な細胞機能傷害と細胞死を引き起こすことを示した。

Report

(2 results)
  • 2007 Annual Research Report
  • 2006 Annual Research Report
  • Research Products

    (39 results)

All 2008 2007 2006

All Journal Article (27 results) (of which Peer Reviewed: 16 results) Presentation (10 results) Book (2 results)

  • [Journal Article] Inflammatory responses of gingival epithelial. cells stimulated with Porphyromonas gingivalis vesicles are inhibited by hop-associated polyphenols.2008

    • Author(s)
      Kou, Y, et. al.
    • Journal Title

      Journal of Periodontology 79(1)

      Pages: 174-180

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Heterogenic virulence and related factors among clinical isolates of Porphyromonas gingivalis with type II fimbriae.2008

    • Author(s)
      Inaba, H, et. al.
    • Journal Title

      Oral Microbiology and Immunology 23(1)

      Pages: 29-35

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Signaling pathways in osteoblast proinflammatory responses to infection by Porphyromonas gingivalis.2008

    • Author(s)
      Ohno, T, et. al.
    • Journal Title

      Oral Microbiology and Immunology 23(in press)

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Porphyromonas gingivalis gingipains cause G1 arrest in osteoblastic/stromal cells.2008

    • Author(s)
      Kato, T, et. al.
    • Journal Title

      Oral Microbiology and Immunology (in press)

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Distribution of Porphyromonas gingivalis fimA genotypes in cardiovascular specimens from Japanese patients.2008

    • Author(s)
      Nakano, K, et. al.
    • Journal Title

      Oral Microbiology and Immunology (in press)

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Molecular interaction of alanine-rich and proline-rich regions of cell surface protein antigen PAc in Streptococcus mutans.2008

    • Author(s)
      Matsumoto-Nakano, M, et. al.
    • Journal Title

      Oral Microbiology and Immunology (in press)

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cellular motility of Down syndrome gingival fibroblasts susceptible to impairment by Porphyromonas gingivalis invasion.2008

    • Author(s)
      Murakami, J, et. al.
    • Journal Title

      Journal of Periodontology (in press)

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] P.gingivalis accelerates gingival epithelial cell progression through the cell cycle.2008

    • Author(s)
      Kuboniwa, M, et. al.
    • Journal Title

      Microbes and Infection (in press)

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Relationship of Porphyromonas gingivalis with glycemic level in patientswith type 2 diabetes following periodontal treatment.2008

    • Author(s)
      Makiura, N, et. al.
    • Journal Title

      Oral Microbiology and Immunology (in press)

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Identification of hop polyphenolic components which inhibit prostaglandin E_2 production by gingival epithelial cells stimulated with periodontal pathogen.2008

    • Author(s)
      Inaba, H, et. al.
    • Journal Title

      Biological & Pharmaceutical Bulletin (in press)

    • NAID

      110006623088

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Upregulation of S100 calcium-bingding protein by periodontal pathogen. Porphyromonas gingivalis,is the critical cause of intimal hyperplasia in the aorta.2008

    • Author(s)
      Hokamura, K, et. al.
    • Journal Title

      Circulation (in press)

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Serotype distribution of Streptococcus mutans a pathogen of dental caries in cardiovascular specimens from Japanese patients2007

    • Author(s)
      Nakano, K, et. al.
    • Journal Title

      Journal of Medical Microbiology 56(4)

      Pages: 551-556

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Maturation of fimbria precursor protein by exogenous gingipains in Porphyromonas gigivalis gingipain-null mutant.2007

    • Author(s)
      Kato, T, et. al.
    • Journal Title

      FEMS Microbiology Letters 273

      Pages: 96-102

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Zinc-finger transcription factor Odd-skipped related 2 is one of the regulators in osteoblast proliferation and bone formation.2007

    • Author(s)
      Kawai, S, et. al.
    • Journal Title

      The Journal of Bone and Mineral Research 22(9)

      Pages: 1362-1372

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Disruption of epithelial barrier and impairment of cellular function by Porphyromonas gingivalis.2007

    • Author(s)
      Amano, A
    • Journal Title

      Frontiers in Bioscience 12

      Pages: 3965-3974

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 糖尿病と歯科骨粗鬆症2007

    • Author(s)
      天野敦雄、河合伸治
    • Journal Title

      CLINICAL CALCIUM 17(2)

      Pages: 186-191

    • Related Report
      2007 Annual Research Report
  • [Journal Article] Detection of novel serotype k Streptococcus mutans in infective endocardites patients.2007

    • Author(s)
      Nakano, K, et. al.
    • Journal Title

      Journal of Medical Microbiology 56(10)

      Pages: 1413-1415

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Distribution of genotypes of Porphyromonas gingivalis in type 2 diabetic patients with periodontitis in Mexico.2007

    • Author(s)
      Davila-Perez C et al.
    • Journal Title

      Journal of Clinical Periodontology 34・1

      Pages: 25-30

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Virulence of Porphyromonas gingivalis is altered by substitution of fimbria gene with different genotype.2007

    • Author(s)
      Kato T et al.
    • Journal Title

      Cellular Microbiology 9・3

      Pages: 753-765

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Detection and serotype distribution of Actinobacillus action-mycetemcomitans in cardiovascular specimens from Japanese patients.2007

    • Author(s)
      Nakano K et al.
    • Journal Title

      Oral Microbiology and Immunology 22・2

      Pages: 136-139

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Serotype distribution of Streptococcus mutans, a pathogen of dental caries, in cardiovascular specimens from Japanese patients.2007

    • Author(s)
      Nomura R et al.
    • Journal Title

      Journal of Medical Microbiology 56・3

      Pages: 1135-1140

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Proinflammatory gene expression in mouse ST2 osteoblast/stromal cell line in response to infection by Porphyromonas gingivalis.2006

    • Author(s)
      Ohno T et al.
    • Journal Title

      Microbes and Infection 8・4

      Pages: 1025-1034

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Inhibitory effects of tumor necrosis factor-α on migration of human periodontal ligament cells.2006

    • Author(s)
      Takemura A et al.
    • Journal Title

      Journal of Periodontology 77・5

      Pages: 883-890

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Invasion of epithelial cells and proteolysis of cellular focal adhesion components by distinct fimbria types of Porphyromonas gingivalis.2006

    • Author(s)
      Nakagawa I et al.
    • Journal Title

      Infection and Immunity 74・7

      Pages: 3773-3782

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Isolation and characterization of Streptococcus mutans in heart valve and dental plaque specimens from a patient with infective endocarditis.2006

    • Author(s)
      Nomura R et al.
    • Journal Title

      Journal of Medical Microbiology 55・8

      Pages: 1135-1140

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Detection of cariogenic Streptococcus mutans in extirpated heart valve and atheromatous plaque specimens.2006

    • Author(s)
      Nakano K et al.
    • Journal Title

      Journal of Clinical Microbiology 44・9

      Pages: 3313-3317

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Autophagy in innate immunity against intracellular bacteria2006

    • Author(s)
      Amano A et al.
    • Journal Title

      Journal of Biochemistry 140・2

      Pages: 161-166

    • NAID

      10018842714

    • Related Report
      2006 Annual Research Report
  • [Presentation] P. gingivalis II型線毛株の細胞傷害性2008

    • Author(s)
      天野敦雄
    • Organizer
      特定領域研究「学術フロンティア」2007年度班会議
    • Place of Presentation
      千葉県松戸市
    • Year and Date
      2008-08-17
    • Related Report
      2007 Annual Research Report
  • [Presentation] Sharing of roles by cellular A5B1 integrin and lipid to internalize Porphyromonas gingivlis2007

    • Author(s)
      Furnta, N, et. al.
    • Organizer
      International symposium "Membrane Traffic"
    • Place of Presentation
      淡路島
    • Year and Date
      2007-12-26
    • Related Report
      2007 Annual Research Report
  • [Presentation] Starategy of Porphyromonas gingivalis for periodontal destruction.2007

    • Author(s)
      Amano, A
    • Organizer
      Osaka University - UCSF Joint Symposium in San Francisco
    • Place of Presentation
      San Francisco, USA
    • Year and Date
      2007-11-28
    • Related Report
      2007 Annual Research Report
  • [Presentation] ビールホップポリフェノールによる歯周炎症の抑制2007

    • Author(s)
      天野敦雄, 他
    • Organizer
      第24回日本障害者歯科学会学術大会
    • Place of Presentation
      長崎市
    • Year and Date
      2007-11-24
    • Related Report
      2007 Annual Research Report
  • [Presentation] 歯肥大発症因子のDNAマイクロアレイ解析2007

    • Author(s)
      加藤隆大, 他
    • Organizer
      第24回日本障害者歯科学会学術大会
    • Place of Presentation
      長崎市
    • Year and Date
      2007-11-24
    • Related Report
      2007 Annual Research Report
  • [Presentation] Effect of genotypes of Porphyromonas gingivalis fimbriae on biofilm formation2007

    • Author(s)
      Kuboniwa, M, et. al.
    • Organizer
      55th Annual Meeting of Japanese Association for Dental Research
    • Place of Presentation
      横浜
    • Year and Date
      2007-11-17
    • Related Report
      2007 Annual Research Report
  • [Presentation] Ors1 gene expression is regulated by Runx2 and Ikaros transcription factors2007

    • Author(s)
      Yamauchi, M, et. al.
    • Organizer
      29th Annual Meeting of the American Society of Bone and Mineral Research
    • Place of Presentation
      Honolulu, USA
    • Year and Date
      2007-09-17
    • Related Report
      2007 Annual Research Report
  • [Presentation] Odd-skipped related 2 functions in cell proliferation2007

    • Author(s)
      Kawai, S, et. al.
    • Organizer
      29th Annual Meeting of the American Society of Bone and Mineral Research
    • Place of Presentation
      Honolulu, USA
    • Year and Date
      2007-09-17
    • Related Report
      2007 Annual Research Report
  • [Presentation] Hop-polyphenol prevents cellular inflammatory responses.2007

    • Author(s)
      Kou, Y, et. al.
    • Organizer
      8th Annual Scientific Meeting of IADR Chinese Division
    • Place of Presentation
      Xi'an, China
    • Year and Date
      2007-09-14
    • Related Report
      2007 Annual Research Report
  • [Presentation] Molecular interaction between periodontal bacteria and gingival epiithelial cells.2007

    • Author(s)
      Amano, A
    • Organizer
      Egypt-Japan Scientific Collaboration Conference
    • Place of Presentation
      Alexandria, Egypt
    • Year and Date
      2007-05-31
    • Related Report
      2007 Annual Research Report
  • [Book] 歯科医学の最先端2008

    • Author(s)
      天野敦雄, 他4名(分担)
    • Total Pages
      321
    • Publisher
      大阪大学出版会
    • Related Report
      2007 Annual Research Report
  • [Book] Autophagy eliminates group A Streptococcus invading host cells. p. 139-150. (In Deretic V (ed.)) (Autophagy in Immunity and Infection.)2006

    • Author(s)
      Amano A, Yoshimori T
    • Total Pages
      22
    • Publisher
      WILEY-VCH Verlag GmbH & Co. KGaA
    • Related Report
      2006 Annual Research Report

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Published: 2006-04-01   Modified: 2018-03-28  

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