Inhibition of excessive scleroderma fibroblast collagen production by recombinant γ‐interferon: Association with a coordinate decrease in types I and III procollagen messenger RNA levels

Abstract

The effects of recombinant γ-interferon (rec γ-IFN) on collagen production by confluent monolayer cultures of progressive systemic sclerosis (PSS) dermal fibroblasts were studied. Five cell lines obtained from patients with rapidly progressive disease of recent onset were examined. All PSS fibroblast cell lines exhibited increased collagen production when compared with normal skin cell lines. It was found that rec γ-IFN caused potent inhibition of PSS fibroblast collagen production in a concentration-dependent manner. Greater than 50% inhibition was observed with as little as 50 antiviral units/ml, and maximal effects were attained at a concentration of 500 units/ml. The rec γ-IFN caused reproducible inhibition of collagen production by the 5 PSS fibroblast cell lines, ranging from 58.9% to 85.6% of control values. Measurement of type I and type III procollagen messenger RNA (mRNA) levels with specific complementary DNA probes demonstrated a coordinate reduction of >60% in mRNA for both transcripts in rec γ-IFN-treated cells, compared with control cells. These findings indicate that rec γ-IFN can modulate the excessive collagen biosynthesis characteristic of PSS fibroblasts and that this effect can be explained largely by the γ-IFN-mediated decrease in specific collagen mRNAs.