Regulation of Collagen Synthesis and mRNA Expression in Normal and Hypertrophic Scar Fibroblasts in Vitro by Interferon-γ

Development of hypertrophic scarring (HTS) is a major problem for patients who survive extensive thermal injuries. HTS and other fibroproliferative disorders are associated with excessive accumulation of collagen and other extracellular matrix proteins. Recent in vitro and in vivo studies have demonstrated that proteins of the interferon family have an inhibitory effect on collagen production by fibroblasts in some fibroproliferative disorders. This study investigated the effects of interferon-γ (IFN-γ) 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 explants of biopsies obtained from HTS and normal skin (matched for location 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-γ (1000 U/ml) to proliferating fibroblast cultures for 5 days resulted in 51% reduction ( P < 0.05) in HTS cell proliferation. Using hydroxyproline as an index for collagen production, a 34% reduction ( P < 0.05) in collagen synthesis was observed in HTS fibroblast culture media after treatment with IFN-γ (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, respectively, after treatment for 12 hr with IFN-γ (1000 u/ml). The effect of IFN-γ on each of these parameters was at least as pronounced in HTS fibroblasts as their normal controls. These results suggest that IFN-γ has a down-regulatory effect on cell proliferation and collagen production in fibroblasts from patients with HTS, a condition resulting from excess collagen synthesis and deposition within the extracellular matrix. Improved understanding of such regulatory mechanisms may eventually be of therapeutic significance in the control of HTS.