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2004 Fiscal Year Final Research Report Summary

Regulation of signal transduction through toll like receptors (interleukin-1 receptor related) by stimulation of live Mycobacterium tuberculosis

Research Project

Project/Area Number 14572111
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Environmental pharmacy
Research InstitutionNagoya City University

Principal Investigator

TAKII Takemasa  Molecular Health Sciences, Graduate School of Pharmaceutical Sciences, Instructor, 大学院・薬学研究科, 助手 (80244573)

Co-Investigator(Kenkyū-buntansha) ONOZAKI Kikuo  Molecular Health Sciences, Graduate School of Pharmaceutical Sciences, Professor, 大学院・薬学研究科, 教授 (20101313)
Project Period (FY) 2002 – 2004
Keywordstuberculosis / interleukin 1 / toll like receptor / fibroblast / cytokine
Research Abstract

We have previously revealed that live, but not dead, Mycobacterium tuberculosis exhibits cytotoxicity to human lung fibroblast cell line (J. Interferon Cytokine Res., 2001, Antimicrob. Agents Chemother., 2002). In order to investigate the signal transduction from live bacteria to host cell, we studied the expression of toll like receptors (TLRs), which are related to interleukin 1 receptor (IL-1R), and signal transduction from the receptors after stimulation with live bacilli. Lipoproteins which are present in cell wall of mycobacteria are reported as major ligand to TLR2 and induces apoptosis of macrophages. Lipopolysaccharide present in cell wall of gram-negative bacteria, transducer its signal through TLR4. In this study, LPS and transforming growth factor beta are revealed to regulate the expression of TLR2 and TLR4 on mouse hepatocyte (Immunology, 2003, J. Leukocyto Biol., 2004). Human fibroblast cell line, MRC-5, is known to constitutively expresses TLR1-10. The mechanism of activation of NF-kB is closely related to that of IL-1R. Therefore, we have investigated the activation of NF-kB on MRC-5 after stimulation of live M. tuberculosis. Live, but not dead, bacilli strongly induces NF kB and also induce expression of inflammatrical cytokines. Interestingly, the kinetics of induction of NF-kB and cytokines are similar to that of the effect of cytotoxicity of live bacilli. These data suggests that the signaling from TLRs after stimulation of live bacilli would have significance on the cytotoxicity to human cell. Further, we were also successful in applying the cytotoxicity testing for susceptibility test to pyrazinamic acid using clinical isolates of tuberculosis (Antimicrob. Agents Chemother., 2005)

  • Research Products

    (14 results)

All 2005 2004 2003 2002

All Journal Article (14 results)

  • [Journal Article] Simple fibroblast-based assay to test the pyrazinamide susceptibility of Mycobacterium tuberculosis.2005

    • Author(s)
      Takii T, Hamasaki S, Hirano K, Abe C, Onozaki K
    • Journal Title

      Antimicrob Agents Chemother 49・2

      Pages: 804-807

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Pyrazinamic acid susceptibility test of Mycobacterium tuberculosis by simple fibroblast assay2005

    • Author(s)
      Takii.T., Hamasaki, S., Hirano, K., Abe, C., K.Onozaki
    • Journal Title

      Antimicrob. Agents Chemother. 49(2)

      Pages: 804-807

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Polycyclic aromatic hydrocarbon increases mRNA level for interleukin 1 beta in human fibroblast-like synoviocyte line via aryl hydrocarbon receptor.2004

    • Author(s)
      Tamaki A, Hayashi H, Nakajima H, Takii T, Katagiri D, Miyazawa K, Hirose K, Onozaki K
    • Journal Title

      Biol Pharm Bull 27・3

      Pages: 407-410

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] TGF-beta down-regulates IL-1alpha-induced TLR2 expression in murine hepatocytes.2004

    • Author(s)
      Matsumura T, Hayashi H, Takii T, Thorn CF, Whitehead AS, Inoue J, Onozaki K
    • Journal Title

      J Leukocyto Biology 75・6

      Pages: 1056-1061

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Polycyclic aromatic hydrocarbon increases mRNA level for interleukin 1 beta in human fibroblast-like synoviocyte line via aryl hydrocarbon receptor2004

    • Author(s)
      Tarnaki, A., Hayashi, H., Nakajima, H., Takii, T., Katagiri, D., Miyazawa, K., Hirose, K., K.Onozaki
    • Journal Title

      Biol. Pharm. Bull. 27(3)

      Pages: 407-410

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] TGF-β down-regulates IL-1α-induced TLR2 expression in murine hepatocytes2004

    • Author(s)
      Matsumura, T., Hayashi, H., Takii, T., Thom, C.F., Whitehead, A.S., Inoue, J., K.Onozaki
    • Journal Title

      J. Leuko. Biol. 75(6)

      Pages: 1056-1061

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Multiple mechanisms involved in the inhibition of proinflammatory cytokine production from human monocytes by N-(p-coumaroyl)serotonin and its derivatives.2003

    • Author(s)
      Takii T, Kawashima S, Chiba T, Hayashi H, Hayashi M, Hiroma H, Kimura H, Inukai Y, Shibata Y, Nagatsu A, Sakakibara J, Oomoto Y, Hirose K, Onozaki K
    • Journal Title

      Int Immunopharmacol 3・2

      Pages: 273-277

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] TRAF6-NF-kappaB pathway is essential for interleukin-1-induced TLR2 expression and its functional response to TLR2 ligand in murine hepatocytes.2003

    • Author(s)
      Matsumura T, Degawa T, Takii T, Hayashi H, Okamoto T, Inoue J, Onozaki K
    • Journal Title

      Immunology 109・1

      Pages: 127-136

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Multiple mechanisms involved in the inhibition of proinflammatory cytokine production from human monocytes by N (p-coumaroyl)serotonin and its derivatives2003

    • Author(s)
      Takii, T., Kawashima, S., Chiba, T., Hayashi, H., Hayashi, M., Hiroma, H., Kimura, H., Inukai, Y., Shibata, Y., Nagatsu, A., Sakakibara, J., Oomoto, Y., Hirose, K., K.Onozaki
    • Journal Title

      Inter. Immunopharmacology 3(2)

      Pages: 273-277

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] TRAF-6-NF-kB pathway is essential for IL-1-induced TLR2 expression and its functional response to TLR2 ligand in murine hepatocytes2003

    • Author(s)
      Matsumura, T., Degawa, T., Takii, T., Hayashi, H., Okamoto, T., Inoue, J., K.Onozaki
    • Journal Title

      Immunology 109(1)

      Pages: 127-136

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Simple fibroblast-based assay for screening of new antimicrobial drugs against Mycobacterium tuberculosis2002

    • Author(s)
      Takii T, Yamamoto Y, Chiba T, Abe C, Belisle JT, Brennan PJ, Onozaki K
    • Journal Title

      Antimicrob Agents Chemother 46・8

      Pages: 2533-2539

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Novel 33-kilodalton lipoprotein from Mycobacterium leprae2002

    • Author(s)
      Maeda Y, Makino M, Crick DC, Mahapatra S, Srisungnam S, Takii T, Kashiwabara Y, Brennan PJ
    • Journal Title

      Infect Immun 70・8

      Pages: 4106-4111

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Simple fibroblast-based assay for screening of new antimicrobial drugs against Mycobacterium tuberculosis2002

    • Author(s)
      Takii, T., Yamamoto, Y., Chiba, T., Abe, C., Belisle, J.T., Brennan, P.J., K.Onozaki
    • Journal Title

      Antimicrob. Agents Chemother 46(8)

      Pages: 2533-2539

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Novel 33-kilodalton lipoprotein from Mycobacterium leprae2002

    • Author(s)
      Maeda, Y., Makino, M., Crick, D.C., Mahapatra, S., Srisungnam, S., Takii, T., Kashiwabara, Y., P.J.Brennan
    • Journal Title

      Infect. Immun. 70(8)

      Pages: 4106-4111

    • 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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