| Project/Area Number |
13226042
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| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | Kyoto University |
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Principal Investigator |
MITSUYAMA Masao Kyoto University, Graduate School of medicine, Professor, 大学院・医学研究科, 教授 (10117260)
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| Co-Investigator(Kenkyū-buntansha) |
河村 伊久雄 京都大学, 医学研究科, 助教授 (20214695)
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| Project Period (FY) |
2001 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥55,600,000 (Direct Cost: ¥55,600,000)
Fiscal Year 2005: ¥15,000,000 (Direct Cost: ¥15,000,000)
Fiscal Year 2004: ¥15,000,000 (Direct Cost: ¥15,000,000)
Fiscal Year 2003: ¥15,600,000 (Direct Cost: ¥15,600,000)
Fiscal Year 2002: ¥10,000,000 (Direct Cost: ¥10,000,000)
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| Keywords | intracellular parasitic bacteria / Listeria monocvtogenes / Mycobacterium tuberculosis / macrophage / cytokine / listeriolysin O / リステリア / γインターフェロン / アポトーシス / ネクローシス / 細胞内寄生 / カスパーゼ / 病原因子 / エスケープ |
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| Research Abstract |
(1) Listeriolysin 0 (LLO) is the major virulence factor of Listeria monocytogenas a representative intracellular parasitic bacteria, and exhibits a strong cytokine-inducing activity in addition to its role for the escape of this bacterium by cytolytic activity in the host macrophaes. Our study dearly showed that the cytokine-inducing activity, especially gammainterferon-inducing activity is dependent on the N-terminus while the cytolytic activity depends on the C-terminus
(2) It was shown that all the cytokine-inducing CDC family proteins including LW filbt activate macrophages far IL-12 and IL-18 and. these macrophage-derived cytokines in turn stimulate NK cells for gamma interferon production that is essential for the induction of Thl-dependent protective immunity
(3) There is a significant difference in the cytokine-inducing ability among LLO and allied proteins produced by Listeria seeligeri and Listeria ivanovii. We were able to show that such a difference is highly dependent on the structural difference at the N-terminus domain. A contribution of unique molecule recognizing LLO inside macrophage cytosol was also suggested.
(4) Thl cytokine induction by Mycobacterium tuberculosis requires the stimulation with viable bacteria. It was shown that some growing bacteria-derive factor that depends on bacterial metabolism is required.
(5) In experimental model of allergic condition in mice, LLO and allied protein with Thl cytokine-inducing activity were effective for the alleviation and control of allergic response.
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