Topical administration of the pan-Src kinase inhibitors, dasatinib and LCB 03-0110, prevents allergic contact dermatitis in mice

Title
Topical administration of the pan-Src kinase inhibitors, dasatinib and LCB 03-0110, prevents allergic contact dermatitis in mice
Authors
정승희Xiaoyan SunRyu WS양범석
Keywords
allergic contact dermatitis; pan-Src kinase inhibitor; dasatinib; LCB 03-0110; atrophy
Issue Date
2013-01
Publisher
British journal of dermatology
Citation
VOL 168, NO 1, 112-119
Abstract
Background:  Allergic contact dermatitis (ACD) is a delayed type of T cell-mediated cutaneous inflammatory response, in which multiple cell types are involved. Dasatinib and LCB 03-0110 are small molecule multi-tyrosine kinase inhibitors, and they share remarkably similar target kinases such as the c-Src family, Btk, and Syk, which play key roles in the cell signaling of T cells and other inflammatory cells. Objective:  The anti-ACD activity of dasatinib and LCB 03-0110 were tested and compared to that of tacrolimus (FK506) and triamcinolone acetonide (a glucocorticoid), which are widely used for topical treatment of ACD. Moreover, the 2 compounds were examined for their capacity to induce skin atrophy, a side effect. Methods:  ACD was induced on the ears of mice by repeated topical application of oxazolone. Each test compound was then topically applied on the ear. Ear swelling, epidermal thickness, and levels of inflammatory cytokines were measured. The skin atrophy induced by the compounds was tested during prolonged application on the dorsal skin of hairless mice, followed by hematoxylin and eosin staining. Results:  Dasatinib and LCB 03-0110 suppressed the symptoms of ACD such as ear swelling, increase in epidermal thickness, and synthesis of inflammatory cytokines (i.e., IL-1β, TNF-α, and IFN-γ) in a dose-dependent manner. The 2 compounds showed near-equal potency to tacrolimus; however, their potency was lesser than that of triamcinolone acetonide. Prolonged treatment with the 2 compounds did not induce any skin atrophy, although use of steroidal agents induced it severely. Conclusions:  Dasatinib and LCB 03-0110 could be used as effective agents for the treatment of ACD without the adverse side effect of skin atrophy.
URI
http://pubs.kist.re.kr/handle/201004/44663
ISSN
00070963
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KIST Publication > Article
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