Functional analysis of RIP1 using 3D cultured epidermal model - Is 'keratosis' a necroptosis? -

2016 Fiscal Year Final Research Report

• Project/Area Number: 15K19669
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Dermatology
• Research Institution: Asahikawa Medical College
• Principal Investigator: SAITO Nao 旭川医科大学, 医学部, 研究生 (90736670)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Keywords: RIP1 / 尋常性乾癬

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.

Free Research Field

皮膚科学