Plasminogen activator and prostaglandin E2 levels in human synovial fibroblasts. Differential stimulation by synovial activator and other cytokines.
Interaction between cells of the immune system and of the synovial tissue may be contributing to the pathogenesis of rheumatoid arthritis. Cytokines, produced by PBMC, were tested for their effects on plasminogen activator activity and PGE2 levels of a number of human synovial fibroblast-like cell lines. Evidence was obtained for a human monocyte polypeptide, synovial activator, which can stimulate synovial cell plasminogen activator activity but not PGE2 levels. Purified human rIL-1 alpha and IL-1 beta increased the levels of both products in the supernatants of the synovial cells; TNF-alpha raised the PGE2 levels but raised the plasminogen activator activity only weakly and inconsistently. Synovial activator was further distinguished from IL-1 alpha and IL-1 beta (and TNF-alpha) on biochemical, immunologic, and functional criteria. No other purified native or recombinant human cytokine tested was active on the synovial cells when judged by the criteria in question. Synovial activator could therefore be a novel monokine. The differences in the type of response elicited by the various cytokines in the synovial fibroblast-like cells could have implications for the understanding of the cellular interactions occurring in rheumatoid lesions.
Leizer
T
T
Department of Medicine, University of Melbourne, Parkville, Australia.
Hamilton
J A
JA
D002478:Cells, Cultured; D003470:Culture Media; D015232:Dinoprostone / Q000378:metabolism*; D005337:Fibrin; D005347:Fibroblasts / Q000201:enzymology / Q000378:metabolism*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D010960:Plasminogen Activators / Q000378:metabolism*; D013379:Substrate Specificity; D013583:Synovial Membrane / Q000201:enzymology / Q000378:metabolism*; D014020:Tissue Extracts / Q000302:isolation & purification / Q000502:physiology*
D003470:Culture Media; D007375:Interleukin-1; D014020:Tissue Extracts; D005337:Fibrin; D010960:Plasminogen Activators; D015232:Dinoprostone