Increases in levels of procollagenase messenger RNA in cultured fibroblasts induced by human recombinant interleukin 1 beta or serum follow c-jun expression and are dependent on new protein synthesis.

The protein encoded by the protooncogene c-jun, included in the activator protein-1 (AP-1) complex, is probably the critical trans-acting factor controlling transcription of the procollagenase gene which is rate limiting for subsequent synthesis of procollagenase. Therefore, to elucidate possible mechanisms whereby IL-1 stimulates procollagenase synthesis, we measured levels of c-jun and procollagenase mRNA in human serum-starved dermal fibroblasts in response to human recombinant IL-1 beta (hrIL-1 beta). hrIL-1 beta or serum induced rapid increases in c-jun mRNA levels; mRNA levels declined rapidly after hrIL-1 beta and more slowly after exposure to serum. The increases in levels of c-jun mRNA preceded the increases in procollagenase mRNA. Whereas the increases in levels of procollagenase mRNA were blunted by cycloheximide, those of c-jun mRNA were enhanced. We interpret these results as follows: IL-1 or serum induce transcription of c-jun by mechanisms independent of new protein synthesis; c-JUN, the protein product of c-jun in the AP-1 complex, is an essential mediator of the effects of IL-1 or serum in the subsequent induction of expression of the procollagenase gene.