Characterization of a novel BCG-derived TLR2 ligand capable of preferentially inducing Th1 cytokine production and investigation of the cytokine-inducing mechanism
| Project/Area Number |
15590385
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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 |
Bacteriology (including Mycology)
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| Research Institution | Kyoto University |
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Principal Investigator |
KAWAMURA Ikuo Kyoto University, Graduate School of Medicine, Associate Professor, 医学研究科, 助教授 (20214695)
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| Co-Investigator(Kenkyū-buntansha) |
MITSUYAMA Masao Kyoto University, Graduate School of Medicine, Professor, 医学研究科, 教授 (10117260)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2004: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2003: ¥2,600,000 (Direct Cost: ¥2,600,000)
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| Keywords | Mycobacterium tuberculosis / BCG / IFN-γ / IL-12 / Ferritin / 結核菌 / マクロファージ / Toll-like receptor / Mycobacterium bovis BCG / NF-κB / ハイドロキシアパタイト |
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| Research Abstract |
Among various inflammatory cytokines produced at the early stage of infection with Mycobacterium bovis BCG, Interferon-γ plays a pivotal role for development of protective T cells. We have shown that IFN-γ production is induced by both IL-12 and IL-18 that are produced from macrophages infected with BCG or M.tuberculosis(MTB), and that some mycobacterial factor in the culture supernatant contributes to IL-12p40 production via activation of Toll-like Receptor 2(TLR2) pathway. Because IL-12p40, a subunit of IL-12, is an important factor for IFN-γ induction, it seems that IL-12p40-inducing mycobacterial component plays a critical role in generation of protective immunity. To identify the factor, we prepared a culture filtrate(CF) from 1d-culture of MTB and fractionated CF by gel filtration chromatography. The strong activity was found in the fractions containing molecules of MW 150-200k and the fractions were able to induce activation of NF-κB via TLR2 pathway. By SDS-PAGE analysis under nonreducing condition, we detected about 190kDa and 200kDa proteins in the fractions. The proteins were extracted from the gel and SDS-PAGE analysis was performed under reducing condition. The size of those proteins was shifted to 22k and 19k, respectively, indicating that those proteins in the culture supernatant are composed of each small subunit. We further found that 19k molecule was a mycobacterial ferritin familiy protein, Brf2. Those results suggest that the mycobacterial ferritin protein probably contribute to IL-12p40 induction via activation of TLR2 pathway.
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Report
(3 results)
Research Products
(13 results)
