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
| Project/Area Number |
14572111
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Environmental pharmacy
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| Research Institution | Nagoya City University |
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Principal Investigator |
TAKII Takemasa Molecular Health Sciences, Graduate School of Pharmaceutical Sciences, Instructor, 大学院・薬学研究科, 助手 (80244573)
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| 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)
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| Project Period (FY) |
2002 – 2004
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| Keywords | tuberculosis / interleukin 1 / toll like receptor / fibroblast / cytokine |
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| 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)
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[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
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Journal Title
Biol. Pharm. Bull. 27(3)
Pages: 407-410
Description
「研究成果報告書概要(欧文)」より
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[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
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Journal Title
J. Leuko. Biol. 75(6)
Pages: 1056-1061
Description
「研究成果報告書概要(欧文)」より
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[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
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Journal Title
Int Immunopharmacol 3・2
Pages: 273-277
Description
「研究成果報告書概要(和文)」より
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[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
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Journal Title
Inter. Immunopharmacology 3(2)
Pages: 273-277
Description
「研究成果報告書概要(欧文)」より
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[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
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Journal Title
Immunology 109(1)
Pages: 127-136
Description
「研究成果報告書概要(欧文)」より
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[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
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Journal Title
Antimicrob. Agents Chemother 46(8)
Pages: 2533-2539
Description
「研究成果報告書概要(欧文)」より
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[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
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Journal Title
Infect. Immun. 70(8)
Pages: 4106-4111
Description
「研究成果報告書概要(欧文)」より
