Cycloheximide induces stromelysin mRNA in cultured human fibroblasts

Abstract

Stromelysin is a metalloproteinase that degrades extracellular matrix macromolecules including fibronectin, laminin, collagen IV and proteoglycans. We now report that cycloheximide, an inhibitor of protein synthesis, induces human stromelysin mRNA in fibroblast cultures in a time- and dose-dependent fashion. As determined by Northern hybridization, a 24-h treatment with cycloheximide increased stromelysin mRNA about 20-fold over the control level. In vitro translation or translation in cells after removal of cycloheximide resulted in increased levels of immunoprecipitable stromelysin suggesting that the cycloheximide-induced stromelysin mRNA was functional. Analysis of mRNA stability suggested that the cycloheximide effect is in part due to the increased activation of the stromelysin gene. In contrast to these results, cycloheximide did not induce collagenase mRNA but, rather, prevented its induction by interleukin-1 beta. These data provide evidence for discoordinate regulation of collagenase and stromelysin genes and suggest that a short-lived repressor protein may play a role in the stromelysin gene expression.