| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Outline of Final Research Achievements |
Receptor-interacting protein kinase 1 (RIP1) regulate inflammatory signaling in response to stimuli, such as TNF-α, TRAIL, and TLRs, resulting in apoptosis, necroptosis and NF-κB activation. However, the physiological relevance in human epidermis remains elusive.
In this study, we examined whether RIP1 is involved in the pathogenesis of psoriasis. In lesional psoriatic epidermis, RIP1-expression was decreased compared with normal epidermis. In addition, RIP1-knockdown enhanced TRAIL-mediated expression of psoriasis-related cytokines, such as IL-1β, IL-6, IL-8, TNF-α, in HEK. Moreover, TRAIL-neutralization in an imiquimod-induced murine psoriasis model remarkably improved skin phenotype, such as ear thickness, and TNF-α expression in lesional skin. Collecting these results, we conclude that TRAIL-mediated downregulation of RIP1 plays a critical role in the pathogenesis of psoriasis vulgaris via positive regulation of psoriasis-related cytokine-expression.
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