Gene expression is differently affected by pimecrolimus and betamethasone in lesional skin of atopic dermatitis.

ABSTRACT: Topical corticosteroids and calcineurin inhibitors are well known treatments of atopic dermatitis (AD), but differ in their efficacy and side effects. A study in AD patients has demonstrated that betamethasone valerate (BM) though clinically more efficient impaired skin barrier repair in contrast to pimecrolimus. Objective: The present study elucidates the mode of action of topical BM and pimecrolimus cream in AD. Methods: These two components were subjected to gene expression profile analysis in lesional AD skin after topical treatment. Results: BM resulted in a significant reduction of mRNA levels of genes encoding for markers for dendritic cells, T cells, cytokines, chemokines and serine proteases, whereas pimecrolimus exerted minor effects only. This corroborates the clinical finding that BM reduces inflammation more effectively than pimecrolimus. Genes encoding molecules important for skin barrier function were differently affected. Both BM and pimecrolimus normalized the expression of filaggrin and loricrin. BM, but not pimecrolimus, significantly reduced the expression of rate-limiting enzymes for lipid synthesis and the expression of involucrin and small proline-rich proteins, which covalently bind ceramides. This may explain the lack of restoration of functional stratum corneum layers observed after BM treatment. Conclusion: The gene expression profiles are consistent with previous findings that corticosteroids may exert a more potent anti-inflammatory effect but may impair the restoration of the skin barrier. Hence, this study confirms the hypothesis at the molecular level that corticosteroids are a suitable treatment for acutely exacerbated AD, but that pimecrolimus is preferable for long-term treatment and stabilization.

ORGANISM(S): Homo sapiens

PROVIDER: GSE32473 | GEO | 2011/09/30

SECONDARY ACCESSION(S): PRJNA147695

REPOSITORIES: GEO