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Can periodontopathic bacteria induce the cytokines production that cause atherosclerosis in ApoE knockout mice ?

Research Project

Project/Area Number 14370608
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field 病態科学系歯学(含放射線系歯学)
Research InstitutionTokyo Dental College

Principal Investigator

OKUDA Katsuji  Tokyo Dental College, Dentistry, Professor, 歯学部, 教授 (40085741)

Co-Investigator(Kenkyū-buntansha) KATO Tetsuo  Tokyo Dental College, Dentistry, Assistant Professor, 歯学部, 助教授 (00159253)
ISHIHARA Kazuyuki  Tokyo Dental College, Dentistry, Assistant Professor, 歯学部, 助教授 (00212910)
YAMANAKA Ayumi  Tokyo Dental College, Dentistry, Assistant, 歯学部, 助手 (40231667)
KIMIZUKA Ryuta  Tokyo Dental College, Dentistry, Assistant, 歯学部, 助手 (90287178)
本間 聖進  東京歯科大学, 歯学部, 助手 (50338860)
Project Period (FY) 2002 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥9,600,000 (Direct Cost: ¥9,600,000)
Fiscal Year 2005: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 2004: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 2003: ¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 2002: ¥2,900,000 (Direct Cost: ¥2,900,000)
KeywordsPeriodontal diseases / Periodontopathic bacteria / Atherosclerosis / ApoE / Knockout mice / Cytokine / Porphyromonas gingivalis / Treponema denticola / 歯周病原細菌 / バイオフィルム / 炎症性サイトカイン / ApoEノックアウトマウス / 細胞侵入 / Porphyromonas gingivaris
Research Abstract

Circulatory disorders such as atherosclerosis involve very complex factors such as hyperlipidemia, obesity, smoking, and genetic factors. It has been clarified in recent years that microbial infections invades the vascular endothelial cells, and triggers atherosclerosis at the invasion site. In consequence, atherosclerosis has been considered to relate a microbial infection-induced inflammatory disorder. Epidemiological studies have shown the relationship between periodontal disease and ischemic arterial disease. Postulated mechanisms to link periodontal disease-associated biofilm and vascular disease are shown in many research groups. We detected periodontopathic Treponema denticola in samples of atherosclerosis lesions. We extracted DNA from embedded arterial disease samples and investigated the presence of T.denticola 16S rRNA in 6 aneurysm lesions. When the samples were stained with specific anti-T.denticola antibody, we observed aggregated antigenic particles reacting with the antibody in and around foam cells in aneurysms. In cooperation with a heart surgery center, we extracted DNA from plaque samples from coronary arterial walls at the sites of arterosclerosis lesions, and investigated the presence of specific DNA of Porphyromonas gingivalis, Actinobacillus actinomycetemcomitans, Tannerella forsythensis, Campylobacter rectus and T.denticola. We concluded that detections of P.gingivalis and Crectus from coronary disease sites were closely related with their infections in periodontal sites. We demonstrated that the cells of T. denticola produced IL-8, and ICAM-1 from human umbilical vein epithelial cells. These findings suggest that periodontopathic bacterial affect the cytokine network that plays a significant role to control homeostasis results in the trigger or relates to inflammatory responses.

Report

(5 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • 2003 Annual Research Report
  • 2002 Annual Research Report
  • Research Products

    (43 results)

All 2006 2005 2004 2003 2002 Other

All Journal Article (32 results) Book (3 results) Publications (8 results)

  • [Journal Article] Periodontopathic bacterial endotoxin-induced tumor necrosis factor a production was inhibited by excerise in mice.2006

    • Author(s)
      Kato T
    • Journal Title

      FEMS Immunol Medical Microbiol. (In press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] The Treponema denticola surface protease dentilisin degrades interleukin-1B,IL-6, and tumor necrosis factor a2006

    • Author(s)
      Miyamoto M
    • Journal Title

      Infect Immun (In press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] The Treponema denticola surface protease dentilisin degrades interleukin-1 β, IL-6, and tumor necrosis factor α2006

    • Author(s)
      Miyamoto M
    • Journal Title

      Infect Immun (In press)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Salivary bisphenol-A levels detected by ELISA after restoration with composite resin.2005

    • Author(s)
      Sasaki N
    • Journal Title

      J Mater Sci Mater Med 16

      Pages: 297-300

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Murine monoclonal antibody which can distinguish cystatins SA1 and SA22005

    • Author(s)
      Ito T
    • Journal Title

      Mol Immunol 42

      Pages: 1259-1263

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Detection of heat shock proteins but not superantigen by isolated oral bacteria from patients with Behcet's disease2005

    • Author(s)
      Miura T
    • Journal Title

      Oral Microbiol. Immunol. 20

      Pages: 167-171

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Immunization by Arg-gingipain A DNA vaccine protevts mice against an invasive Porphyromonas gingivalis infection through regulation of interferon-r production.2005

    • Author(s)
      Yonezawa H
    • Journal Title

      Oral Microbio. Immunol. 2

      Pages: 259-266

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Involvement of periodontopathic anaerobes in aspiration pneumonia2005

    • Author(s)
      Okuda K
    • Journal Title

      J. Periodontol. 76

      Pages: 2154-2160

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Salivary bisphenol-A levels detected by ELISA after restoration with composite resin.2005

    • Author(s)
      Sasaki N, Okuda K, Kato T, Kakishima H, Okuma H, Abe K, Tachino H, Tuchida K, Kubono K
    • Journal Title

      J.Mater.Sci.Mater.Med. 16

      Pages: 297-300

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Murine monoclonal antibody which can distinguish cystatins SA1 and SA22005

    • Author(s)
      Ito T, Komiya-Ito A, Okuda K, Minaguchi K, Saitoh E, Yamada S., Kato T
    • Journal Title

      Mol.Immunol. 42

      Pages: 1259-1263

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Detection of heat shock proteins but not superantigen by isolated oral bacteria from patients with Behcet's disease.2005

    • Author(s)
      Miura T, Ishihara K, Kato T, Kimizuka R, Miyabe H, Ando T, Uchiyama, T, Okuda K
    • Journal Title

      Oral Microbiol.Immunol. 20

      Pages: 167-171

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Immunization by Arg-gingipain A DNA vaccine protevts mice against an invasive Porphyromonas gingivalis infection through regulation of interferon-γ production2005

    • Author(s)
      Yonezawa H, Kato T, Kuramitsu H K, Okuda K, Ishihara K
    • Journal Title

      Oral Microbiol.Immunol. 20

      Pages: 259-266

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Involvement of periodontopathic anaerobes in aspiration pneumonia2005

    • Author(s)
      Okuda K, Kimizuka R, Abe S, Kato T, Ishihara K
    • Journal Title

      J Periodontol. 76

      Pages: 2154-2160

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Salivary bisphenol-A levels detected by ELISA after restoration with composite resin2005

    • Author(s)
      Sasaki, N.
    • Journal Title

      J.Mater.Sci.Mater.Med. 16・4

      Pages: 297-300

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Murine monoclonal antibody which can distinguish cystatins SA1 and SA2.2005

    • Author(s)
      Ito, T.
    • Journal Title

      Mol.Immunol. 42・10

      Pages: 1259-1263

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Detection of heat shock proteins but not superantigen by isolated oral bacteria from patients with Behcet's disease.2005

    • Author(s)
      Miura, T.
    • Journal Title

      Oral Microbiol.Immunol. 20・3

      Pages: 167-171

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Immunization by Arg-gingipain A DNA vaccine protevts mice against an invasive Porphyromonas gingivalis infection through regulation of interferon-γ production.2005

    • Author(s)
      Yonezawa, H.
    • Journal Title

      Oral Microbiol.Immunol. 20・4

      Pages: 259-266

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Involvement of periodontopathic anaerobes in aspiration pneumonia2005

    • Author(s)
      Okuda, K.
    • Journal Title

      J.Periodontol. 76・11

      Pages: 2154-2160

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Correlation between the detection of periodontopathic bacterial DNA in carotid coronary stenotic arlery plaque with dental plaque2004

    • Author(s)
      Ishihara K
    • Journal Title

      J. Clin. Microbiol 42

      Pages: 1313-1315

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Need for procedural details in detection of periodontopathic bacterial DNA in the atheroscrematous plaque by PCR2004

    • Author(s)
      Ishihara K
    • Journal Title

      J Clin Microbiol 42

      Pages: 4914-4915

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Correlation between the detection of periodontopathic bacterial DNA in carotid coronary stenotic artery plaque with dental plaque.2004

    • Author(s)
      Ishihara K, Nabuchi A, Ito R, Miyachi K, Kuramitsu H., Okuda K.
    • Journal Title

      J.Clin.Microbiol. 42

      Pages: 1313-1315

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Need for procedural details in detection of periodontopathic bacterial DNA in the atheroscrematous plaque by PCR2004

    • Author(s)
      Ishihara K, Nabuchi A, Ito R, Miyachi K, Kuramitsu H., Okuda K.
    • Journal Title

      J Clin Microbiol. 42

      Pages: 4914-4915

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Correlation between the detection of periodontopathic bacterial DNA in coronary stenotic artery plaque with dental plaque2004

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

      Journal Clinical Microbiology 42

      Pages: 1313-1315

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Need for procedural details in detection of periodontopathic bacterial DNA in the atheroscrematous plaque by PCR.2004

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

      Journal Clinical Microbiology 42

      Pages: 4914-4915

    • Related Report
      2004 Annual Research Report
  • [Journal Article] A 43 kDa protein of Treponema denticola is essential for dentilisin activity.2004

    • Author(s)
      Ishihara et al.
    • Journal Title

      FEMS Microbiol.Lett 232

      Pages: 181-188

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Cystatin SA, a cystatine proteinase inhibitor, induces gamma interferon expression in2004

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

      Biol Chem 385

      Pages: 419-422

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Mixed infection with Porphyromonas gingivalis and Trepnema denticola causes excessive inflammatory responses in a mouse pneumonia model compared with monoinfection.2003

    • Author(s)
      Kimizuka R
    • Journal Title

      Micro. Infect 5

      Pages: 1357-1362

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Mixed infection with Porphyromonas gingivalis and Trepnema denticola causes excessive inflammatory responses in a mouse pneumonia model compared with monoinfection.2003

    • Author(s)
      Kimizuka R, Kato T, Ishihara K., Okuda K.
    • Journal Title

      Micro.Infect. 5

      Pages: 1357-1362

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Mixed infection with Porphyromonas gingivalis and Treponema denticola cause excessive inflammatory responses in a mouse pneumonia model compared2003

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

      Microbes and Infection 5

      Pages: 1357-1362

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Salivary cystatins induced interleukin-6 expression via cell surface molecules2002

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

      Molecular Immunology 39

      Pages: 423-430

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Periodontopathic bacterial endotoxin-induced tumor necrosis factor a production was inhibited by excerise in mice.

    • Author(s)
      Kato T, Kaneko S, Kimizuka R., Okuda K.
    • Journal Title

      FEMS Immunol Medical Microbiol. (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] The Treponema denticola surface protease dentilisin degrades interleukin-1b, IL-6, and tumor necrosis factor alpha,

    • Author(s)
      Miyamoto M, Ishihara K., Okuda K.
    • Journal Title

      Infect Immun. (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Book] 唾液による健康づくり2005

    • Author(s)
      奥田克爾
    • Total Pages
      215
    • Publisher
      ヒョーロンバブリシャー
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Book] 唾液による健康づくり2005

    • Author(s)
      奥田克爾
    • Total Pages
      215
    • Publisher
      ヒョーロンパブリシャー
    • Related Report
      2005 Annual Research Report
  • [Book] 口腔内バイオフィルム2004

    • Author(s)
      奥田克爾
    • Total Pages
      212
    • Publisher
      医歯薬出版
    • Related Report
      2004 Annual Research Report
  • [Publications] Kimizuka R, Okuda K: "Mixed infections with Porphyromonas gingivalis and Treponema denticola cause excessive inflammatory responses in a mouse pneumonia model compared with monoinfections"Microbes and Infection. 5. 1357-1362 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Asano, Okuda K: "relationship between transmission of Porphyromonas gingivalis and FimA type in spouses"J.Periodontology. 74. 1355-1360 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Koto T, Okuda K: "Salivary cystatins induced interleukin-6 expression via cell surface monecules"Molecular Immunology. 39. 423-430 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] Adachi M, Okuda K: "Effect of professional oral health care on elderly living in nursing homes"Oral Sur.Oral Med. Oral Path.Oral Rad.. 94. 191-195 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] 奥田 克爾: "最新口腔微生物学"一世出版. 460 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] Koto T, Okuda K: "Salivary cystatins induced interleukin-6 expiession via cell surface monecules"Molecular Immunology. 39. 423-430 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Adachi M, Okuda K: "Effect of professional oral health care on elderly living in nursing homes"Oral Sur. Oral Med. Oral Path.. 94. 191-195 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 奥田 克爾: "最新口腔微生物学"一世出版. 460 (2002)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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