Immune interferon suppresses levels of procollagen mRNA and type II collagen synthesis in cultured human articular and costal chondrocytes

Cultured human articular and costal chondrocytes were used as a model system to examine the effects of recombinant γ-interferon (IFN-γ) on synthesis of procollagens, the steady state levels of types I and II procollagen mRNAs, and the expression of major histocompatibility complex class II (Ia-like) antigens on the cell surface. Adult articular chondrocytes synthesized mainly type II collagen during weeks 1-3 of primary culture, whereas types I and III collagens were also produced after longer incubation and predominated after the first subculture. Juvenile costal chondrocytes synthesized no detectable α2(I) collagen chains until after week 1 of primary culture; type II collagen was the predominant species even after weeks of culture. The relative amounts of types I and II collagens synthesized were reflected in the levels of α1(I), α2(I), and α1(II) procollagen mRNAs. In articular chondrocytes, the levels of α1(I) procollagen mRNA were disproportionately low (α1(I)/α2(I) < 1.0) compared with costal chondrocytes (α1(I)/α2(I) ~ 2). Recombinant IFN-γ (0.1-100 units/ml) inhibited synthesis of type II as well as types I and III collagens associated with suppression of the levels of α1(I), α2(I), and α1(II) procollagen mRNAs. IFN-γ suppressed the levels of α1(I) and α1(II) procollagen mRNAs to a greater extent than α2(I) procollagen mRNA in articular but not in costal chondrocytes. Human leukocyte interferon (IFN-α) at 1000 units/ml suppressed collagen synthesis and procollagen mRNA levels to a similar extent as IFN-γ at 1.0 unit/ml. In addition, IFN-γ but not IFN-α induced the expression of HLA-DR antigens on intact cells. The lymphokine IFN-γ could, therefore, have a role in suppressing cartilage matrix synthesis in vivo under conditions in which the chondrocytes are in proximity to T lymphocytes and their products.