Effects of cyclosporin and ultraviolet radiation on growth and ornithine decarboxylase activity in cultured human epidermal keratinocytes.

Abstract

Both cyclosporin (CyA) and ultraviolet radiation are effective in the treatment of psoriasis, but their precise mechanisms of action are uncertain. We investigated their effects on ornithine decarboxylase (ODC) activity, ODC gene expression, and cellular proliferation stimulated by epidermal growth factor (EGF), in cultured normal human epidermal keratinocytes. CyA (5 micrograms/ml) inhibited ODC activity, ODC mRNA level, and cell growth induced by 50 ng/ml EGF. Ultraviolet B (10 mJ/cm2) irradiation suppressed the induction of ODC, ODC mRNA, and cell proliferation stimulated by EGF, but ultraviolet A (0-15 J/cm2) irradiation inhibited neither EGF-stimulated ODC activity nor cell proliferation. These findings indicate that reduction of ODC activity in CyA- or ultraviolet B-treated human keratinocytes may contribute to the antiproliferative mechanism of these agents. These results also suggest that the regulation of ODC activity by ultraviolet B and A irradiation may be mediated by different signal transduction pathways.