The CYP26 inhibitor R115866 potentiates the effects of all-trans retinoic acid on cultured human epidermal keratinocytes.

摘要: Summary Background  All-trans retinoic acid (RA) is known to regulate keratinocyte proliferation and differentiation, retinoids are used as therapeutic agents in certain dermatological disorders, such psoriasis acne. Epidermal expression of the heparin-binding epidermal growth factor-like factor (HB-EGF) induced by RA treatment HB-EGF responsible for RA-mediated hyperplasia vivo. also induces cultured keratinocytes alters their differentiating phenotype. R115866 a specific inhibitor cytochrome P450 isoform CYP26, which involved metabolic inactivation pathway RA. Thereby, thought be able increase intracellular levels endogenous RA. Objectives  To determine whether or not potentiates effect low concentrations on keratinocytes. Methods  We analysed HB-EGF, involucrin keratin 10 mRNA protein autocrine human cultures incubated 18 h with alone combinations. Results  concentration-dependent manner, whereas it inhibited expression. had no these genes. However, when was combined RA, induced. Conclusion  These results strongly suggest that effects present at concentrations.