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

Abstract

protein, or isotretinoin-induced TUNEL-positive signals are detectable in sebocytes in the basal and suprabasal layers, but not so or less so in fully differentiated sebocytes in humans in vitro and in vivo (18,19).In conclusion, we put forward novel evidence that DHS exhibit apoptosis resistance by the intracellular increase in store-operated Ca 2+ release, which causes the loss of Ca 2+ influx. Finally, these findings should accelerate the understanding of the mechanisms of sebogenesis and/or sebum production and secretion under physiological conditions. AcknowledgementsThis work was supported in part by a Grant-in-Aid for Scientific Research (C) (#22590506) (To T. S.) and by a grant to private universities provided by The Promotion and Mutual Aid Corporation for Private Schools of Japan. T. S. and A. I. designed the research study and reviewed the data. H. K. and N. A. performed the research and analysed the data. T. S. wrote the study. All authors read and approved the final manuscript. Conflict of interestsThe authors have declared no conflicting interests. Supporting InformationAdditional Supporting Information may be found in the online version of this article: Figure S1. Increase of intracellular Ca 2+ in differentiated hamster sebocytes. Figure S2. Abstract: 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 clobetasoltreated 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.

Nanomiemgel - A Novel Drug Delivery System for Topical Application - In Vitro and In Vivo Evaluation

“…The skin is an exceptionally effective barrier and it prevents the permeation of most of the drugs applied for therapeutic purposes [10] , [11] . Very few drugs have the capability to permeate in significant amounts through the skin.…”

The topical corticosteroid classification called into question: towards a new approach

“…This ex vivo model is probably more reliable and specific than the VCA to assess the antipruritus and anti‐inflammatory effects of TCS . Similarly, as examples, the comparison of TCS may be based on antiproliferative effect assessed by specific skin cells staining ; on skin barrier disruption ; on inflammatory cells infiltration or spongiosis visualised with confocal microscopy; or even on inflammatory mediators released such as IL‐6, adenosine or prostaglandins quantified by microdialysis.…”

Wheat germ agglutinin as a counterstain for immunofluorescence studies of equine hoof lamellae

“…Once noted, the use of WGA as a counterstain enabled us to precisely elucidate the location of antibody binding with greater ease and confidence than we had previously been able to do, providing a rapid, economical and simple counterstain to immunofluorescence studies on equine hoof lamellae. WGA counterstain may also prove useful in dermatological immunofluorescence studies, such as recently published studies of genetic and acquired human epidermal diseases , mouse models of human epidermal disease and complex epidermal tissues in other species .…”