Different effects of topical corticosteroid and topical calcineurin inhibitor on the epidermal tight junction

Abstract

Topical steroids are the mainstay in the treatment of atopic dermatitis (AD), however, their adverse effects on permeability barrier limit their long-term application. Topical agent-induced barrier disruption can trigger exacerbations of AD, therefore the potential for barrier disruption is an important factor when choosing topical therapy. Epidermal tight junctions (TJs) are an another functional barrier of the skin in addition to the stratum corneum, however, the effects of topical steroid and TCIs on TJs have not been reported yet. We therefore investigated the structural changes of TJs in mice skin after topical treatment with 0.1% tacrolimus or 0.05% clobetasol propionate ointment twice daily for 10 days. Hematoxylin and eosin and Masson''s trichrome staining demonstrated that clobetasol propionate led to epidermal thinning and a decrease of dermal collagen density. Confocal immunofluorescence, western blot, and real-time polymerase chain reaction revealed that clobetasol propionate significantly decreased claudin-1, -4, and occludin expression, whereas, tacrolimus did not affect claudin-1 and -4 but downregulated occludin to a lesser extent compared to that of clobetasol propionate -treated skin. In conclusion, we suggest that topical corticosteroids, but not TCIs negatively affect TJ proteins expression, therefore, TCIs are favorable to not only the stratum corneum barrier but also TJ barrier compared to corticosteroids.