Interleukin-1 release by rat synovial cells is dependent on sequential treatment with gamma-interferon and lipopolysaccharide.
To determine the potential regulatory mechanisms involved in synovial cell interleukin-1 (IL-1) release, the ability of gamma-interferon (gamma-IFN) to influence IL-1 release was assessed. Rat synovial cells cultured in the presence of a variety of stimuli, including lipopolysaccharide (LPS), failed to release IL-1. However, pretreatment of synovial cells with gamma-IFN, followed by LPS stimulation, resulted in increased levels of intracellular IL-1 as well as release of IL-1 from the cell. The level of IL-1 release was dependent on the concentration of both gamma-IFN and LPS, and on length of exposure to the gamma-IFN. The kinetic and dose requirements for gamma-IFN-dependent IL-1 release were similar to those for Ia antigen expression, but LPS was necessary for IL-1 messenger RNA induction, intracellular IL-1 accumulation, and IL-1 release. In addition, sequential treatment, i.e., gamma-IFN followed by LPS, was essential for IL-1 induction. Substitution of phorbol ester or calcium ionophore for gamma-IFN did not result in similar IL-1 release. In addition, induction of IL-1 messenger RNA by another stimulus was not sufficient to result in IL-1 release following LPS treatment. These results suggest that release of IL-1 by rat synovial cells requires the production of a regulatory signal, which is inducible by gamma-IFN.
Johnson
W J
WJ
Department of Immunology, Smith Kline & French Laboratories, King of Prussia, PA 19406-0939.
Breton
J
J
Newman-Tarr
T
T
Connor
J R
JR
Meunier
P C
PC
Dalton
B J
BJ
D000818:Animals; D002478:Cells, Cultured; D003470:Culture Media; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D007371:Interferon-gamma / Q000494:pharmacology*; D007375:Interleukin-1 / Q000032:analysis / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D012333:RNA, Messenger / Q000187:drug effects; D051381:Rats; D013583:Synovial Membrane / Q000166:cytology / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors
D003470:Culture Media; D000949:Histocompatibility Antigens Class II; D007375:Interleukin-1; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D007371:Interferon-gamma; D013755:Tetradecanoylphorbol Acetate