| Project/Area Number |
14570431
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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 |
内科学一般
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| Research Institution | Teikyo University School of Medicine |
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Principal Investigator |
HIROHATA Shunsei Teikyo University, Internal Medicine, Associate Professor, 医学部, 助教授 (90189895)
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| Co-Investigator(Kenkyū-buntansha) |
KIKUCHI Hirotoshi Teikyo University, Internal Medicine, Assistant Professor, 医学部, 助手 (80338681)
MIYASHITA Taku Teikyo University, Internal Medicine, Assistant Professor, 医学部, 助手 (00239401)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2003: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2002: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | CD154 / T cell / mRNA / SLE / IFN-α / Jurkat / luciferase / IL-12 / stability / B細胞 / 固相化抗CD3抗体 / 抗CD28抗体 |
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| Research Abstract |
Like IL-12, IFN-α has been found to play an important role in human Th1 responses. Whereas IL-12 enhances CD154 expression on human T cells, the effect of IFN-α has not been elucidated. The present study examined the effects of IFN-α on CD154 expression in human CD4+ T cells, with special attention to the relationship with Th1 responses. IFN-α suppressed CD154 protein and mRNA expression in CD4+ T cells at the initial phase of activation with immobilized anti-CD3, but thereafter enhanced it irrespective of the presence of IL-12. By contrast, IFN-α by itself did not enhance IFN-γ production or mRNA expression in CD4+ T cells in the absence of IL-12, whereas it enhanced it in the presence of IL-12. Either IFN-α or IL-12 did not influence the stability of CD154 mRNA in anti-CD3 activated CD4+ T cells. Rather luciferase assays using a reporter vector containing the CD154 promoter region demonstrate that both IFN-α and IL-12 upregulate the transcription of CD154 mRNA. These results indicate that IFN-α directly enhances CD154 expression in CD4+ T cells by up-regulating the transcription of CD154 mRNA independently of the induction of IFN-γ mRNA expression. The data also suggest that the optimal induction of human Th1 responses by IFN-α might require the presence of IL-12.
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