POSTTRANSCRIPTIONAL REGULATION OF UV INDUCED TNF-ALPHA EXPRESSION

Ultraviolet (UV) irradiation exerts multiple effects on skin cells, in cluding the induction of several cytokines involved in immunomodulatio n. Specifically, UV irradiation has been shown to upregulate the level of tumor necrosis factor-alpha (TNF-alpha) mRNA in keratinocytes. To determine whether the induction of TNF-alpha mRNA is regulated by tran scriptional or post-transcriptional mechanisms, we examined cells of k eratinocytic lineage (SCC12F) for steady state level, transcription ra te, and stability of TNF-alpha mRNA after UV irradiation. Within 4 h t here was a 20-40-fold induction of TNF-alpha mRNA that persisted at lo wer levels through 48 h. Consistently, TNF-alpha protein secretion inc reased at 24 and 48 h after UV irradiation, UV irradiation increased t he half-life of TNF-alpha mRNA from approximate to 35 min to approxima te to 10 h. Conversely, the transcription rate of the TNF-alpha gene i ncreased < 2-fold at the time of peak mRNA steady state levels, Thus, post-transcriptional mechanisms play a major role in UV induced TNF-al pha transcript level.