Direct and indirect modulation of ornithine decarboxylase and cyclooxygenase by UVB radiation in human skin cells

Exposure to solar ultraviolet (UV) B radiation is responsible for skin infl ammation and tumour progression. Cyclooxygenase and ornithine decarboxylase are believed to be involved in such processes since they participate in th e synthesis of mediators of inflammation and cell differentiation, respecti vely. We have investigated the in vitro modulation of expression of such ge nes by UVB radiation in different skin cell lines. We have observed that ac cumulation of ornithine decarboxylase mRNA is unaffected by even high UVB d oses in both human epidermal keratinocytes and dermal fibroblasts, whereas cyclooxygenase-2 levels were significantly up-regulated by low UVB doses in KB human epidermoid keratinocytes. Depletion of total intracellular glutat hione levels in KB cells amplified the activation, revealing a role for an oxidative component of UVB in modulating cyclooxygenase gene expression. Tr ansfer of medium from UVB irradiated keratinocytes to fibroblasts resulted in a significant activation of cyclooxygenase expression and activity, whil e ornithine decarboxylase levels were unaffected. We conclude that UVB radi ation can activate cyclooxygenase gene expression in human skin cells both by direct activation pathways or indirectly by inducing a paracrine mechani sm.