| Project/Area Number |
14570800
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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 |
Dermatology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
KOMINE Mayumi (2002, 2004) The University of Tokyo, Faculty of Medicine, Lecturer, 医学部附属病院, 講師 (00282632)
小宮根 真弓 (2003) 東京大学, 医学部附属病院, 講師 (50215406)
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| Co-Investigator(Kenkyū-buntansha) |
KAKINUMA Takashi The University of Tokyo, Faculty of Medicine, Assistant, 医学部附属病院, 助手 (30332604)
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| Project Period (FY) |
2002 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2004: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2003: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2002: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Keywords | Keratinocytes / Chemokines / TARC / CCL17 / NF kappa B / STAT1 / Inflammatory skin diseases / Mechanical Stress / MAP kinases / CTACK / 転写因子 / HaCaT細胞 / 炎症 / デコイ型核酸 |
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| Research Abstract |
Thymus and activation-regulated chemokine (TARC/CCL17) is a potent chemokine, deeply associated with the pathogenesis of several inflammatory skin diseases, such as atopic dermatitis and bullous pemphigoid. Production of TARC from HaCaT keraitnocytes was synergistically induced by the stimulated with TNFα and IFNγ. NFkB and p38 are indispensable, EGF receptor was negatively involved, and STAT1 was not involved in this induction. PLA2 inhibitor, MAFP, and leukotrien B4 receptor inhibitor, LY, was also effective in suppressing TARC production. IMD, which was produced to suppress NFkB activation was effective in suppressing TARC production from HaCaT keratinocytes. Mechanical stress, are IL-15 are known to induce new lesions in psoriasis. They induced MAP kinase activation, proliferation, and attenuates apoptosis. Mechanical stress induced EGFR phosphorylation, ERK, and AP-1 activation. IL-15 induced ERK and PI3K activation. Suppression of these signaling molecules could be effective in treating inflammatory skin diseases such as psoriasis. We are planning to utilize these possibilities in vivo experiments.
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