IL-1 induces expression of WAF1 mRNA in human fibroblasts: mechanisms of accumulation.

WAF1 inhibits cyclin-cyclin dependent kinase complexes, causing arrest in the cell cycle. We report that interleukin-1 (IL-1) regulates the levels of WAF1 protein and mRNA in human fibroblasts. Further studies showed that 12-O-tetradecanoyl phorbol 13-acetate (TPA) enhanced the accumulation of WAF1; cells refractory to TPA still increased their levels of WAF1 mRNA when exposed to IL-1. IL-1 also increased transcription of WAF1 by 13-fold and WAF1 mRNA became 2-fold more stable in cells stimulated with IL-1 (t1/2 = 2 h) as compared to untreated cells (t1/2 = 1 h). In summary, IL-1 induces expression of WAF1, and this occurs by increased transcription of WAF1 and stabilization of WAF1 mRNA. Our data also indicate that the induction of WAF1 mRNA by IL-1 occurs through a pathway independent of protein kinase C activation.