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2004 Fiscal Year Final Research Report Summary

Studies on recognition mechanism of oral microbes-derived lipopeptides by Toll-like receptors

Research Project

Project/Area Number 15390549
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Morphological basic dentistry
Research InstitutionHokkaido University

Principal Investigator

SHIBATA Ken-ichiro  Hokkaido University, Graduate School of Dental Medicine, Professor, 大学院・歯学研究科, 教授 (50145265)

Co-Investigator(Kenkyū-buntansha) KUROKI Yoshio  Sapporo Medical University, School of Medicine, Professor, 医学部, 教授 (70161784)
YASUDA Motoaki  Hokkaido University, Graduate School of Dental Medicine, associate Professor, 大学院・歯学研究科, 助教授 (90239765)
Project Period (FY) 2003 – 2004
KeywordsToll-like receptor 2 / lipopeptides / lipopeoteins / Leucine-rich repeats / apoptosis
Research Abstract

Toll-like receptor 2 (TLR2)plays a key role in the recognition of microbial lipoproteins/lipoeppetides. However, details in molecular mechanisms of the recognition still remains unknown. This study was therefore carried out to determine the molecular mechanism by which TLR2 recognizes microbial lipoproteins/lipoeppetides.
We have found the following findings.
1.The level of the activity of bacterial triacylated lipopeptides to stimulate macrophages was lower than that of mycoplasmal diacylated lipoepptides.
2.Both lipid and peptide portions of mycoplasmal diacylated lipopeptides are involved in the recognition by TLR2.
3.Leucine residues at positions 107,112 and 115 are involved in the recognition of mycoplasmal lipoproteins/lipopeptide and S.aureus peptidoglycans by TLR2 in combination with TLR6.
4.There is at least one leucine residue in all 8 leucine-rich repeats of TLR2 which is responsible for the the recognition of mycoplasmal lipoproteins/lipopeptide and S.aureus peptidoglycans by TLR2 in combination with TLR6.
5.Leucine residues in β-sheet structure of leucine-rich repeats are involved in the recognition of mycoplasmal lipopeptides by TLR2 in combination with TLR6.
6.Mycoplasmal lipoproteins possesses the activity to induce apoptosis of HEK293 cells through TLR2/TLR2 and the activity is mediated by FADD and MyD88 downstream of TLR2.

  • Research Products

    (12 results)

All 2005 2004 2003

All Journal Article (12 results)

  • [Journal Article] Structure-function relationship of mycoplasmal lipoproteins/lipopeptides and their recognition by Toll-like receptor 2.2005

    • Author(s)
      K Shibata, M Fujita, M Morita
    • Journal Title

      J Oral Biosci 46(3)

      Pages: 203-220

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Stimulation of human Toll-like receptor (TLR) 2 and TLR6 with membrane lipoproteins of Mycoplasma fermentans induces apoptotic cell death after NF-kappaB activation2004

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

      Cell Microbiol 6(2)

      Pages: 187-199

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Relationship between structures and biological activities of mycoplasmal diacylated lipopeptides and their recognition by Toll-like receptors 2 and 6.2004

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

      Infect Immun 72(3)

      Pages: 1657-1665

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Biological activities of Bacteroides forsythus lipoproteins and their possible pathological roles in periodontal disease.2004

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

      Infect Immun 72(3)

      Pages: 1318-1325

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Possible roles of Toll-like receptor 2/6 and extracellular ATP on mycoplasmal membrane lipoprotein-induced cell activation and death.2004

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

      J Oral Biosci 46(4)

      Pages: 278-288

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Structure-function relationship of mycoplasmal lipoproteins/lipopeptides and their recognition by Toll-like receptor 22004

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

      J Oral Biosci 46(3)

      Pages: 203-220

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Stimulation of human Toll-like receptor (TLR) 2 and TLR6 with membrane lipoproteins of Mycoplasma fermentans induces apoptotic cell death after NF-kappaB activation.2004

    • Author(s)
      T Into, K Kiura, M Yasuda, H Kataoka, N Inoue, A Hasebe, K Takeda, S Akira, K Shibata.
    • Journal Title

      Cell Microbiol 6(2)

      Pages: 187-199

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Relationship between structures and biological activities of mycoplasmal diacylated lipopeptides and their recognition by Toll-like receptors 2 and 6.2004

    • Author(s)
      T Okusawa, M Fujita, J Nakamura, T Into, M Yasuda, A Yoshimura, Y Hara, A Hasebe, DT Golenbock, M Morita, Y Kuroki, T Ogawa, K Shibata.
    • Journal Title

      Infect Immun 72(3)

      Pages: 1657-1665

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Biological activities of Bacteroides forsythus lipoproteins and their possible pathological roles in periodontal disease.2004

    • Author(s)
      A Hasebe, A Yoshimura, T Into, H Kataoka, S Tanaka, S Arakawa, H Ishikura, DT Golenbock, T Sugaya, N Tsuchida, M Kawanami, Y Hara, K Shibata
    • Journal Title

      Infect Immun 72(3)

      Pages: 1318-1325

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Possible roles of Toll-like receptor 2/6 and extra cellular ATP on mycoplasmal membrane linonrotein-induced cell activation and death.2004

    • Author(s)
      T Into, K Shibata
    • Journal Title

      J Oral Biosci 46(4)

      Pages: 278-288

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Involvement of leucine residues at positions 107, 112 and 115 in a leucine-rich repeat motif of human Toll-like receptor 2 in the recognition of diacylated lipoproteins and lipopeptides and Staphylococcus aureus peptidoglycans2003

    • Author(s)
      M.Fujita et al.
    • Journal Title

      J Immunol 171

      Pages: 3675-3683

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Involvement of leucine residues at positions 107,112 and 115 in a leucine-rich repeat motif of human Toll-like receptor 2 in the recognition of diacylated lipoproteins and lipopeptides and Staphylococcus aureus peptidoglycans.2003

    • Author(s)
      M Fujita, T Into, M Yasuda, T Okusawa, S Hamahira, Y Kuroki, A Eto, T Nisizawa, M Morita, K Shibata.
    • Journal Title

      J Immunol. 171

      Pages: 3675-3683

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2006-07-11  

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