POSTTRANSCRIPTIONAL REGULATION OF INTERLEUKIN-6 GENE-EXPRESSION IN HUMAN KERATINOCYTES BY ULTRAVIOLET-B RADIATION

Exposure to increasing doses (290-315 nm) of ultraviolet (UV) B radiat ion is thought to profoundly affect human health. Studies on the biolo gic and molecular effects of UVB radiation on human skin are therefore of particular interest. There is experimental and clinical evidence t o assume that UVB radiation-induced local and systemic inflammatory re actions might be mediated at least in part by UVB-induced keratinocyte -derived interleukin (IL)-6. Previously, a UVB-induced increase of ste ady-state levels of IL-6 mRNA was found to be a prerequisite for kerat inocyte IL-6 production after UVB irradiation. The present study was a imed at addressing the question of whether in vitro UVB irradiation wo uld increase IL-6 mRNA expression in long-term cultured, normal human keratinocytes via transcriptional or post-transcriptional mechanisms. UVB exposure (0-100 J/m(2)) of keratinocytes increased low baseline ex pression levels of IL-6 mRNA in a time- and dose-dependent manner. Usi ng nuclear run-on assays, transcription rates of the IL-6 gene in nucl ei isolated from UVB-irradiated cells were found to be essentially ide ntical to those seen in unirradiated cells, indicating that UVB light did not lead to increased transcription of the IL-6 gene. To determine a possible post-transcriptional mechanism in UVB-induced IL-6 mRNA ex pression, the effects of UVB irradiation on IL-6 mRNA stability were e xamined. To this end irradiated and unirradiated keratinocytes were tr eated with actinomycin D and subjected to Northern blot analysis to ca lculate IL-6 mRNA half-life. As compared with unirradiated cells, IL-6 mRNA stability was increased significantly (three- to four-fold) in U VB-irradiated cells, suggesting that UVB radiation upregulates IL-6 mR NA levels in human keratinocytes by increasing the stability of IL-6 t ranscripts. This is the first report indicating that UVB radiation at a physiologically relevant dose may affect gene expression in human ce lls at a post-transcriptional level.