Funding sources This study was supported by the Fusion Technology Development Program through the Small and Medium Business Administration (SD122968) and KIST (2E22760) grant.
Topical administration of the pan-Src kinase inhibitors, dasatinib and LCB 03-0110, prevents allergic contact dermatitis in mice
Article first published online: 21 DEC 2012
© 2012 The Authors. BJD © 2012 British Association of Dermatologists
British Journal of Dermatology
Volume 168, Issue 1, pages 112–119, January 2013
How to Cite
Jung, S.H., Sun, X., Ryu, W.-S. and Yang, B.-S. (2013), Topical administration of the pan-Src kinase inhibitors, dasatinib and LCB 03-0110, prevents allergic contact dermatitis in mice. British Journal of Dermatology, 168: 112–119. doi: 10.1111/bjd.12069
Conflicts of interest None declared.
- Issue published online: 21 DEC 2012
- Article first published online: 21 DEC 2012
- Accepted manuscript online: 28 SEP 2012 10:31AM EST
- Accepted for publication 24 September 2012
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 multityrosine 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 signalling of T cells and other inflammatory cells.
Objectives To test the anti-ACD activity of dasatinib and LCB 03-0110 and compare it with that of tacrolimus (FK506) and triamcinolone acetonide (a glucocorticoid), which are widely used for topical treatment of ACD, and to examine the two compounds 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 haematoxylin 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. interleukin-1β, tumour necrosis factor-α and interferon-γ) in a dose-dependent manner. The two compounds showed near-equal potency to tacrolimus; however, their potency was lower than that of triamcinolone acetonide. Prolonged treatment with the two compounds did not induce any skin atrophy, whereas use of steroidal agents induced severe atrophy.
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.