Selective inhibition of human diploid fibroblast collagen synthesis by interferons

Abstract

The effects of α- and γ-interferons (IFNs) on collagen production by confluent human diploid fibroblasts in culture were examined. It was found that partially purified α-IFNs and affinity purified γ-IFNs caused > 50% inhibition of collagen synthesis by these cells independently of their effect on cell proliferation. Recombinant α-IFNs showed a similar effect (38.8% inhibition), indicating that collagen synthesis inhibition was a constitutive property of IFNs. Collagen synthesis inhibition by IFNs was concentration dependent. Gel filtration chromatography of the newly synthesized proteins from the media of fibroblasts incubated with partially purified α-IFNs demonstrated a selective depression of molecules eluting in the region of procollagen. No detectable increase in collagen degradation products or underhydroxylation of procollagen was observed. Short-term kinetic studies further demonstrated that the major effect of IFNs was due to a net decrease in fibroblast collagen production rather than to impairment of secretion or increased extracellular degradation of the newly synthesized molecules. These results indicate that α- and γ-IFNs are potent inhibitors of human fibroblast collagen production and suggest that they may play an important role in the regulation of normal and pathologic fibrogenesis.