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Clarification of the mechanism of periodontitis-initiated/accelerated atheroacleicsis and identification of its causal components

Research Project

Project/Area Number 18592263
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Periodontal dentistry
Research InstitutionThe University of Tokushima

Principal Investigator

YUMOTO Hiromichi  The University of Tokushima, Institute of Health Biosciences, Graduate School, Assistant professor (60284303)

Co-Investigator(Kenkyū-buntansha) NAKAE Hideaki  The University of Tokushima, Institute of Health Biosciences, Graduate School, Associate professor (30227730)
OZAKI Kazumi  The University of Tokushima, Institute of Health Biosciences, Graduate School, Professor (90214121)
TAKAHASHI Kanako  The University of Tokushima, Institute of Health Biosciences, Graduate School, Assistant professor (80403715)
TAKAMATSU Natsuko  The University of Tokushima, Institute of Health Biosciences, Graduate School, Assistant professor (90403716)
Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥3,860,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥360,000)
Fiscal Year 2007: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2006: ¥2,300,000 (Direct Cost: ¥2,300,000)
KeywordsPeriodontal Disease / Atherosclerosis / Periodontopathogen / Bacterial Infection / Inflammation / Macrophage / Gene_Expression / Immune Reaction / 炎症性サイトカイン / シグナル伝達 / スカベンジャーレセプター
Research Abstract

Emerging basic scientific studies have supported that infection may represent a risk factor for atherosclerosis. With periodotopathogenic bacteria, Porphyromonas gingivalis, as model pathogen, in vivo studies demonstrated that this organism can accelerate atheroma deposition in animal models. In this study, we first try to determine whether P. gingivalis can up-regulate the expression of the receptors for oxidized LDL in macrophage in vitro. We demonstrated that mouse macrophage cell line, J774.A1 cells were induced to express the receptors (SR-A, CD36 and Lox-1) for oxidized LDL by the stimulation with P. gingivalis, heat-killed bacteria or its fimbriae mutants. Moreover, we found that heat shock protein (HSP) 60 was also induced by the stimulation with P. gingivalis at both mRNA and protein levels. These data support that P. gingivalis stimulate macrophage differentiation to foam cells, a necessary initial event in the development of atherosclerotic plaque lesions.
In this study, we i … More nvestigated the mechanisms of pro-inflammatory cytokine inductions in human monocytic cell line (THP-1 cells) by stimulation with recombinant histone-like DNA binding protein (HLP) of Streptococcus intermedius (rSi-HLP): rSi-HLP stimulation-induced production of pro-inflammatory cytokines (IL-8, IL-1β and TNF-α) occurred in a time- and dose-dependent manner. In contrast with the heat-stable activity of DNA binding, the cytokine induction activity of rSi-HLP was heat-unstable. In subsequent studies, rSi-HLP acted cooperatively with lipoteichoic acid, the synthetic Toll-like receptor 2 agonist, Pam3CSK4, and the cytosolic nucleotide binding oligomerization domain 2 receptor agonist, muramyldipeptide. Furthermore, Western blot and blocking assays with specific inhibitors showed that rSi-HLP stimulation induced the activation of cell signal transduction pathways, extracellular signal-regulated kinase 1/2 (ERK1/2) and c-jun N-terminal kinase (JNK).
Collectively, these results demonstrate oral, especially periodotopathic, bacteria can up-regulate inflammatory response and indicate the infection with these bacteria accelerates inflammatory responses, which directly lead to atherosclerosis. Less

Report

(3 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • Research Products

    (30 results)

All 2008 2007 2006

All Journal Article (19 results) (of which Peer Reviewed: 8 results) Presentation (10 results) Book (1 results)

  • [Journal Article] Toll-like receptor 2 plays a critical role in the progression of atherosclerosis that is independent of dietary lipids.2008

    • Author(s)
      XYNYAN LIU, et. al.
    • Journal Title

      Atherosclerosis 196

      Pages: 146-154

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Histone-like DNA binding protein of Streptococcu intermedius induces the expression of pro-inflammatory cytokines in human monocytes via activation of ERK1/2 and JNK pathways.2008

    • Author(s)
      DALI LIU, et. al.
    • Journal Title

      Cellular Microbiology 10

      Pages: 262-276

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Macrophage-Elicited Osteoclastogenesis in Response to Bacterial Stimulation Requires Tbll-like Receptor2 Dependent Tumor Necrosis Factor-α Production.2008

    • Author(s)
      TAKASHI UKAI, et. al.
    • Journal Title

      Infection and Immunity 76

      Pages: 812-819

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Toll-like receptor 2 plays a critical role in the progression of atherosclerosis that is independent of dietary lipids2008

    • Author(s)
      Xinyan, Liu, et. al.
    • Journal Title

      Atherosclerosis 196

      Pages: 146-154

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Histone-like DNA binding protein of Streptococcus intermedius induces the expression of pro-inflammatory cytokines in human monocytes via activation of ERK1/<2> and INK pathways2008

    • Author(s)
      Dali, Liu, et. al.
    • Journal Title

      Cellular Microbiology 10

      Pages: 262-276

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Macrophage-Elicited Osteoclastogenesis in Response to Bacterial Stimulation Requires Toll-like Receptor 2 Dependent Tumor Necrosis Factor-cr Production2008

    • Author(s)
      Takashi, Ukai, et. al.
    • Journal Title

      Infection and Immunity 76

      Pages: 812-819

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Histone-like DNA binding protein of Streptococcus intermedius induces theexpression of pro-inflammatory cytokines in human monocytes via activationof ERK1/2 and JNK pathways.2008

    • Author(s)
      DALI LIU, et. al.
    • Journal Title

      Cellular Microbiology 10

      Pages: 262-276

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Macrophage-Elicited Osteoclastogenesis in Response to Bacterial StimulationRequires Toll-like Receptor 2 Dependent Tumor Necrosis Factor-α Production.2008

    • Author(s)
      TAKASHI UKAI, et. al.
    • Journal Title

      Infection and Immunity 76

      Pages: 812-819

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Soluble products from Eikenella corrodens inducc cell proliferation and expression of interleukin-8 and adhesion molecules in endothelial cells via mitogen-activated protein kinase pathways.2007

    • Author(s)
      HIROMICHI YUMOTO, et. al.
    • Journal Title

      Oral Microbiology and Immunology 22

      Pages: 36-45

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Soluble products from Eikenella corrodens induce cell proliferation and expression of interleukin-8 and adhesion molecules in endothelial cells via mitogen-activated protein kinase pathways2007

    • Author(s)
      Hiromichi, Yumoto, et. al.
    • Journal Title

      Oral Microbiology and Immunology 22

      Pages: 3645-3645

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Soluble products from Eikenella corrodens induce cell proliferation and expression of interleukin-8 and adhesion molecules in endothelial cells via mitogen-activated protein kinase pathways.2007

    • Author(s)
      HIROMICHI YUMOTO et al.
    • Journal Title

      Oral Microbiology and Immunology 22

      Pages: 36-45

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Fimbria-dependent activation of pro-inflammatory molecules in Porphyromonas gingivalis infected human aortic endothelial cells.2006

    • Author(s)
      YUSUKE TAKAHASHI, et. al.
    • Journal Title

      Cellular Microbiology 8-5

      Pages: 738-757

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Roles of the host oxidative immune response and bacterial antioxidant Rubrerythrin during Porphyromonas gingivalis infection.2006

    • Author(s)
      PIOTR MYDEL, et. al.
    • Journal Title

      PLoS Pathogens 2-7

      Pages: 712-725

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Fimbria-dependent activation of pro-inflammatory molecules in Porphyromonas gingivalis infected human aortic endothelial cells2006

    • Author(s)
      Yusuke, Takahashi, et. al.
    • Journal Title

      Cellular Microbiology 8

      Pages: 738-757

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Roles of the host oxidative immune response and bacterial antioxidant Rubrerythrin during Porphyromonas gingivalis infection2006

    • Author(s)
      Piotr, Mydel, et. al.
    • Journal Title

      PLoS Pathogens 2

      Pages: 712-725

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Cardiovascular disease and periodontal disease, Role of infection from periodontal pathogen for the acceleration of atherosclerosis2006

    • Author(s)
      Takanari, Miyamoto, et. al.
    • Journal Title

      the Quintessence 25

      Pages: 174-183

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Fimbria-dependent activation of pro-inflammatory molecules in Porphyromonas gingivalis infected human aortic endothelial cells.2006

    • Author(s)
      YUSUKE TAKAHASHI et al.
    • Journal Title

      Cellular Microbiology 8・5

      Pages: 738-757

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Roles of the host oxidative immune response an dbacterial antioxidant Rubrerythrin during Porphyromonas gingivalis infection.2006

    • Author(s)
      PIOTR MYDEL et al.
    • Journal Title

      PLoS Pathogens 2・7

      Pages: 712-725

    • Related Report
      2006 Annual Research Report
  • [Journal Article] 心臓血管疾患と歯周病-動脈硬化症への歯周病原性細菌感染のかかわり-2006

    • Author(s)
      宮本 貴成 他
    • Journal Title

      the Quintessence 25・5

      Pages: 174-183

    • Related Report
      2006 Annual Research Report
  • [Presentation] Proinflammatory Roles of NOD2 in Human Gingival Fibroblasts2007

    • Author(s)
      IKUKO HOSOKAWA, et. al.
    • Organizer
      第55回 国際歯科研究学会日本部会(JADR)総会・学術大会
    • Place of Presentation
      鶴見大学記念館
    • Year and Date
      2007-11-17
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Proinflammatory Roles of NOD2 in Human Gingival Fibroblasts2007

    • Author(s)
      Ikuko, Hosokawa, et. al.
    • Organizer
      55th Annual Meeting of Japanese Association for Dental Research
    • Place of Presentation
      Yokohama
    • Year and Date
      2007-11-17
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Proinflammatory Roles of NOD2 in Human Gingival Fibroblasts2007

    • Author(s)
      IKUKO HOSOKAWA, et. al.
    • Organizer
      第55回国際歯科研究学会日本部会(JADR)総会・学術大会
    • Place of Presentation
      鶴見大学記念館
    • Year and Date
      2007-11-17
    • Related Report
      2007 Annual Research Report
  • [Presentation] Proinflammatory cytokines are induced in human monocytes in response to exposure to the histone-like protein of Streptococcus intermedius2007

    • Author(s)
      Dali, Liu, et. al.
    • Organizer
      59th Annual Meeting at Chugoku/Shikoku division of Japanese Society of Bacteriology
    • Place of Presentation
      Ube
    • Year and Date
      2007-10-19
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Histone-like DNA binding protein of Streptococcus intermedius induces the expression of pro-inflammatory cytokines in human monocytes via activation of ERK1/2 and JNK pathways2007

    • Author(s)
      DALI LIU, et. al.
    • Organizer
      日本歯周病学会50周年記念大会
    • Place of Presentation
      東京国際フォーラム
    • Year and Date
      2007-09-21
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Histone-like DNA binding protein of Streptococcus intermedius induces the expression of pro-inflammatory cytokines in human monocytes via activation of ERK1/<2> and JNK pathways2007

    • Author(s)
      Dali, Liu, et. al.
    • Organizer
      Japanese Society of Periodontology 50 years memorial meeting
    • Place of Presentation
      Tokyo
    • Year and Date
      2007-09-21
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Histone-like DNA binding protein of Streptococcus intermedius induces theexpression of pro-inflammatory cytokines in human monocytes via activationof ERK1/2 and JNK pathways2007

    • Author(s)
      DALI LIU, et. al.
    • Organizer
      日本歯周病学会50周年記念大会
    • Place of Presentation
      東京国際フォーラム
    • Year and Date
      2007-09-21
    • Related Report
      2007 Annual Research Report
  • [Presentation] 炎症性サイトカインがヒト歯肉上皮細胞間接着機構に及ぼす影響2007

    • Author(s)
      米田 美穂, 他
    • Organizer
      第50回春季日本歯周病学会学術大会
    • Place of Presentation
      横須賀芸術劇場
    • Year and Date
      2007-05-18
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
  • [Presentation] Inflammatory cytokines effect the expression patterns of claudin family, E-cadherin, JAM-A and occuludin in human gingival epithelial cells2007

    • Author(s)
      Miho, Yoneda, et. al.
    • Organizer
      50th Spring Meeting of Japanese Society of Periodontology
    • Place of Presentation
      Yokusuka
    • Year and Date
      2007-05-18
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Proinflammatory cytokines are induced in human monocytes in response to exposure to the histone-like protein of Streptococcus intermedius2006

    • Author(s)
      DALI LIU, et. al.
    • Organizer
      第59回日本細菌学会中国・四国支部総会
    • Place of Presentation
      宇部市文化会館
    • Year and Date
      2006-10-19
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Book] the Quintessence2006

    • Author(s)
      宮本 貴成, 他
    • Publisher
      心臓血管疾患と歯周病-動脈硬化症への歯周病原性細菌感染のかかわり-
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary

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Published: 2006-04-01   Modified: 2016-04-21  

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