Skin-derived antileukoproteinase (SKALP) and epidermal fatty acid-binding protein (E-FABP): two novel markers of the psoriatic phenotype that respond differentially to topical steroid

Abstract

Recently we have described two novel markers for disturbed epidermal differentiation, which are strongly upregulated in psoriatic epidermis: skin-derived antileukoproteinase (SKALP) and epidermal fatty acid-binding protein (E-FABP). No data are available on the kinetics of SKALP and E-FABP expression in vivo and the relation with epidermal growth and differentiation. We used treatment of lesional psoriatic skin with topical steroid as a model to correlate the expression pattern of SKALP and E-FABP with known cell biological events during regression of the psoriatic lesion. Expression of these markers was studied using immunohistochemistry and Northern blot analysis. After 4 weeks of treatment a substantial clinical improvement was induced by the topical steroid, whereas no significant improvement had occurred at the placebo-treated sides. The expression of SKALP following treatment with steroid was nearly undetectable both at the protein and mRNA level. Mitotic activity, as measured by Ki-67 staining, and cytokeratin 16 expression were downregulated to normal levels in the steroid-treated epidermis. In contrast, although there was a marked decrease of E-FABP mRNA, the staining pattern for E-FABP at the protein level was not affected. After 4 weeks of treatment with steroid the complete suprabasal compartment remained positive, even after considerable clinical improvement of the lesion. We conclude that SKALP and cytokeratin 16 are markers that are downregulated even before complete macroscopic clearance of the lesion. The kinetics of E-FABP expression is distinct from the other molecules and lags behind the clinical signs of psoriasis.