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

M. B. Goldring, L. J. Sandell, M. L. Stephenson, S. M. Krane

Research output: Contribution to journalArticle

114 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)9049-9056
Number of pages8
JournalJournal of Biological Chemistry
Volume261
Issue number19
StatePublished - Dec 1 1986

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