UVB Irradiation Alters Cellular Responses to Cytokines: Role in Extracellular Matrix Gene Expression

Abstract

Solar radiation causes cutaneous photodamage characterized by alterations in the quantity and structure of the extracellular matrix. We determined the direct and cytokine-mediated effects of UV irradiation on mRNA levels for two matrix elements, tropoelastin and fibrillin 1. (i) Comparison of normal versus end-stage photodamaged skin failed to reveal differences in these message levels. (ii) Acutely irradiated skin showed suppression of both tropoelastin and fibrillin mRNAs. (iii) UVB irradiation (50 mJ) of cultured skin fibroblasts suppressed fibrillin mRNA by 50%, consistent with a direct effect of radiation. Addition to the cultured fibroblasts of several cytokines upregulated by UVB showed that IL-1alpha had no effect on fibrillin mRNA in unirradiated cells, but in irradiated cells, this cytokine enhanced the suppression of fibrillin mRNA. There were no changes in the message stability, suggesting altered gene transcription. In contrast, UVB had no effect on tropoelastin mRNA levels in cultured fibroblasts, indicating the absence of a direct effect of radiation. IL-1alpha stimulated tropoelastin mRNA 2.8-fold in unirradiated cells, and this stimulation was entirely blocked by UVB. Overall, our results indicate acute suppression of matrix genes by UVB in vivo. The suppression of fibrillin message was a direct effect of UVB on fibroblasts and was augmented by IL-1alpha. Suppression of tropoelastin message by UVB occurred in vitro only in IL-1alpha-stimulated cells. We conclude that UVB substantially alters the pattern of cellular response to cytokines. The interplay between UVB and cytokines is essential to explain the acute responses of matrix genes to UVB in vivo.