Interleukin-1-induced expression of nitric oxide synthase in insulin-producing cells is preceded by c-fos induction and depends on gene transcription and protein synthesis.

The cytokine interleukin 1 beta (IL-1 beta) induces the expression of an isoform of nitric oxide synthase (NOS) in insulin-producing cells which is similar to that expressed in activated macrophages. In the present study we show that IL-1 beta-induced expression of NOS mRNA in these cells is preceded by expression of c-fos mRNA. Moreover, the stimulatory effects of recombinant IL-1 beta on NOS mRNA expression are prevented by co-incubation with an inhibitor of gene transcription (actinomycin D) or an inhibitor of protein synthesis (cycloheximide). These data suggest that IL-1 beta-induced NOS mRNA expression may be mediated by transcription of immediate early response genes, and that c-fos may be one of these genes.