Tumor necrosis factor-alpha induces mRNA for collagenase and TIMP in human skin fibroblasts.

We demonstrated previously that growth promoting factors in general could induce the secretion of interstitial collagenase into the medium of human fibroblast cells (HF). In this study, the effect of tumor necrosis factor-alpha (TNF-alpha) on the induction of collagenase and tissue inhibitor of metalloproteinases (TIMP) was examined. Stimulation of quiescent HF cells with 10 ng/ml TNF-alpha induced the secretion of Mr 57,000, 52,000 procollagenases into the medium. The collagenase activity was elevated 2.8-fold after TNF-alpha treatment. Northern blot analysis of the steady-state mRNA indicated a tenfold elevation of collagenase transcript after 24 h treatment with 10 ng/ml TNF-alpha. The increase in collagenase mRNA was due to transcriptional activation of collagenase gene activity. TIMP mRNA level increased three-fold after TNF-alpha treatment. The activity of TNF-alpha on collagenase and TIMP induction may play an important role in tissue inflammatory, repair and remodeling processes after wound and injury.