TYPE-VI COLLAGEN-SPECIFIC MESSENGER-RNA IS EXPRESSED CONSTITUTIVELY BY CULTURED HUMAN SYNOVIAL FIBROBLASTS AND IS SUPPRESSED BY INTERLEUKIN-1

Objective. Type VI collagen is a prominent constituent of the synovial extracellular matrix. The cellular source of this matrix protein and the identity of local factors in synovium that may regulate its expression have not been delineated, however. We examined the capacity of human fibroblast-like synovial cells to synthesize type VI collagen as well as the effect of interleukin-1 (IL-1) on this expression. Methods. RNA was extracted from cultured human synovial cells derived from patients with rheumatoid arthritis (RA) and osteoarthritis (OA). Northern blots were analyzed using sequence-specific probes, and steady-state messenger RNA (mRNA) levels of the 3 alpha(VI) procollagen chains were measured. The effect of IL-1 treatment on these levels was determined. Results. Abundant expression of 3 characteristic mRNA transcripts, corresponding to the ol (4.2-kb), alpha 2 (3.5-kb), and alpha 3 (8.5-kb) chains of type VI procollagen, was observed in untreated cells derived from RA and OA patients. IL-1 treatment consistently suppressed steady-state mRNA levels for all 3 alpha(VI) procollagen chains in a time- and dose-dependent manner. Tumor necrosis factor cu induced a response similar to that of IL-1, while IL-2 was ineffective in this regard. Indomethacin partially restored alpha(VI) mRNA expression in IL-1-treated cells. Conclusion. These studies provide novel data demonstrating abundant steady-state levels of mRNA transcripts coding for all 3 type VI procollagen polypeptides in human synovial fibroblast-like cells, as well as coordinated down-regulation of these transcripts by IL-1. Local production of IL-1 may thus constitute an important means in vivo of regulating the production of type VI collagen.