Inhibition of IFN-gamma-induced Ia antigen expression on synovial fibroblasts by IL-1.
Naturally occurring substances capable of the negative regulation of class II molecules on synovial fibroblasts may play an important role in controlling the sustained immune processes ongoing in the rheumatoid joint. We report here that rIL-1 is capable of such a negative regulatory process. The simultaneous addition of rIL-1 and rIFN-gamma to rat synovial fibroblasts resulted in decreased Ia Ag and mRNA expression when compared with synovial fibroblasts treated with IFN-gamma alone. Both rIL-1 alpha and rIL-beta inhibited to a similar degree with the level of inhibition being dependent on both the concentration of IL-1 and IFN-gamma. Other cytokines, including IFN-alpha/beta, IL-2, and TNF, had no antagonistic effect on IFN-gamma-induced Ia expression. Time course experiments showed that IL-1 inhibited when present immediately before addition of IFN-gamma or when added during the first 24 h of IFN-gamma stimulation but not at later time points. Indomethacin failed to reverse the IL-1-mediated inhibition, despite the fact that exogenously added PGE2 also inhibited IFN-gamma-induced Ia expression. IL-1 treatment of synovial cells did not alter the ability of IFN-gamma to bind to the cells. These findings provide evidence for a negative regulatory role for IL-1 on synovial fibroblasts independent of PGE2 production and thus suggest that IL-1 is capable of both pro- and antiinflammatory actions within the rheumatoid joint.
Johnson
W J
WJ
Department of Immunology, Smith Kline & French Laboratories, King of Prussia, PA 19406.
Kelley
A
A
Connor
J R
JR
Dalton
B J
BJ
Meunier
P C
PC
D000818:Animals; D015232:Dinoprostone / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D006801:Humans; D007371:Interferon-gamma / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology*; D007700:Kinetics; D051381:Rats; D011917:Rats, Inbred Lew; D011994:Recombinant Proteins / Q000494:pharmacology; D013583:Synovial Membrane / Q000187:drug effects / Q000276:immunology*
D000949:Histocompatibility Antigens Class II; D007375:Interleukin-1; D011994:Recombinant Proteins; D007371:Interferon-gamma; D015232:Dinoprostone