REGULATION OF COLLAGEN-SYNTHESIS AND MESSENGER-RNA EXPRESSION IN NORMAL AND HYPERTROPHIC SCAR FIBROBLASTS IN-VITRO BY INTERFERON-GAMMA

Development of hypertrophic scarring (HTS) is a major problem for pati ents who survive extensive thermal injuries. HTS and other fibroprolif erative disorders are associated with excessive accumulation of collag en and other extracellular matrix proteins. Recent in vitro and in viv o studies have demonstrated that proteins of the interferon family hav e an inhibitory effect on collagen production by fibroblasts in some f ibroproliferative disorders. This study investigated the effects of in terferon-gamma (IFN-gamma) on cell proliferation, collagen production, and expression of types I and III procollagen mRNA in human postburn HTS fibroblasts. Paired fibroblast cultures were established from expl ants of biopsies obtained from HTS and normal skin (matched for locati on and skin tension) in five patients recovering from thermal injuries . Thus, normal dermis from each patient was used as a paired control. Administration of IFN-gamma (1000 U/ml) to proliferating fibroblast cu ltures for 5 days resulted in 51% reduction (P < 0.05) in HTS cell pro liferation. Using hydroxyproline as an index for collagen production, a 34% reduction (P < 0.05) in collagen synthesis was observed in HTS f ibroblast culture media after treatment with IFN-gamma (1000 u/ml) for 48 hr. Northern blot analysis demonstrated 55 and 36% reductions (P < 0.05 for each) in type I and type III procollagen mRNA levels, respec tively, after treatment for 12 hr with IFN-gamma (1000 u/ml). The effe ct of IFN-gamma on each of these parameters was at least as pronounced in HTS fibroblasts as their normal controls. These results suggest th at IFN-gamma has a down-regulatory effect on cell proliferation and co llagen production in fibroblasts from patients with HTS, a condition r esulting from excess collagen synthesis and deposition within the extr acellular matrix. Improved understanding of such regulatory mechanisms may eventually be of therapeutic significance in the control of HTS. (C) 1995 Academic Press, Inc.