| Project/Area Number |
12670140
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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 |
Pathological medical chemistry
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| Research Institution | Kochi Medical School |
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Principal Investigator |
TANIGUCHI Taketoshi Kochi Medical School, Medicine, Associate prof., 医学部, 助教授 (90127944)
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| Co-Investigator(Kenkyū-buntansha) |
FUKUSHIMA Atsuki Kochi Medical School, Medicine, Reseach Associate, 医学部・附属病院, 助手 (40281737)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2001: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2000: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | Helper T cells / MHC class II / phorbol ester (TPA) / IFN-γ / Induction of Th1 and Th2 / Lewis, Brown Norway rats / RT-PCR / cytokines / INFγレセプター / ルイス・プラウンノルウェーラット |
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| Research Abstract |
Lewis rats are prone to T helper (Th)1 immune responses, whereas Brown Norway (BN) rats are susceptible to Th2 immune responses. Yet, the precise mechanism of induction of the different outcome between these two strains remained elusive. We investigated the expression levels of some cytokines, their receptors and accessory molecules, responsible for the polarization of antigen-specific immune response into a predominant Th1 or Th2 profile in Lewis and BN rats. We observed clear differences between these strains in the expression of IL-12p40, which was high in lymph node cells of Lewis rats. Upregulation of the expression of IL-12 receptor β1, β2, IFN-γ receptor α and β genes were more prominent in Lewis rats rather than BN rats. Thus, IL-12 production by macrophages or dendritic cells seems to be essential event for the activation of Th1 cells
To understand the mechanism of Th1 activaion in Lewis rats, we investigates process of antigen-presentation. Human monocytic leukemia THP-1 cells differentiate into macrophage-like cells when treated with 12-O-tetradecanoyl phorbol-13-acetate (TPA). During this process. IFN-γ-inducible expression of HLA-DRα is markedly enhanced. The enhancement of HLA-DRα expression is at least due to the TPA-dependent induction of the IFN-γ receptor genes. We have studied the mechanism of TPA-induced up-regulation of the IFN-γ R1 gene and identified TPA-responsive element in the promoter of IFN-γ receptor gene.
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