Topical Application of BMS-509744, a Selective Inhibitor of Interleukin-2-inducible T cell Kinase, Ameliorates Imiquimod-induced Skin Inflammation in Mice.
In this study, we investigated the effect of the topically administered selective ITK inhibitor BMS-509744 on imiquimod (IMQ)-induced psoriasis-like skin inflammation in mice. Topically administered BMS-509744 ameliorated IMQ-induced psoriasis-like skin inflammation as shown by decreased skin lesions, epidermal thickening, and cell infiltration into the dermis. These suppressive effects occurred with lower numbers of cluster of differentiation antigen-3+ (CD3+) T cells and T helper subset 17 (Th17)-related cytokine expression in IMQ-treated skin. IMQ-induced upregulation of proinflammatory cytokine expression was also inhibited by topical application of BMS-509744 in IMQ-treated skin. Our report showed for the first time that topical application of BMS-509744 ameliorated psoriasis-like skin inflammation in mice, which is likely mediated by the inhibition of T cell activation in the skin lesions.
PMID: 33473072 [PubMed - as supplied by publisher]
Source: Biological and Pharmaceutical Bulletin - Category: Drugs & Pharmacology Authors: Otake S, Otsubaki T, Uesato N, Ueda Y, Murayama T, Hayashi M Tags: Biol Pharm Bull Source Type: research