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

Tight junction (TJ) is one of the functional barriers present in the skin. Although topical corticosteroids and calcineurin inhibitors are used widely for atopic dermatitis, the effect of these agents on TJs has not been reported. We investigated the structural changes of TJs in mice skin after application of 0.05% clobetasol propionate or 0.1% tacrolimus ointment for 10 days. Clobetasol caused epidermal thinning and decreased collagen density. Basal transepidermal water loss was significantly increased in clobetasol-treated versus vehicle- or tacrolimus-treated skin. Confocal immunofluorescence showed that clobetasol altered the structure of claudin-1,-4 and occludin. Tacrolimus also caused morphological alteration of occludin. Western blot and real-time PCR revealed that clobetasol significantly decreased claudin-1,-4 and occludin, whereas tacrolimus did not significantly affect claudin-1 and -4 but downregulated occludin to a lesser extent compared to clobetasol. In conclusion, we suggest that downregulation of TJ proteins expression is another pathomechanism of corticosteroid-induced permeability barrier disruption.ope