Superantigen-induced stromelysin production from rheumatoid synovial cells.
Superantigens activate a large number of T cells in a V beta-restricted manner after binding to MHC class II molecules on the antigen presenting cells (APC). Superantigens also activate APC directly by interacting with their ligands, MHC class II molecules. In the present study, we examined the effects of superantigens on matrix metalloproteinases (MMPs) secretion from rheumatoid synovial fibroblasts. We demonstrated that stimulation of interferon (IFN)-gamma-treated synovial fibroblasts with staphylococcal enterotoxin A (SEA) selectively induced the secretion of stromelysin, a neutral MMP, from synovial fibroblasts. Pretreatment of synovial fibroblasts with cycloheximide, an inhibitor of protein synthesis, prevented MMP-3 secretion from rheumatoid synovial cells suggesting that protein synthesis was required for SEA-induced MMP-3 secretion after SEA binding to MHC class II molecules. Our data suggest that in the synovium, bacterial superantigens are potent inducers of stromelysin which plays a critical role in articular destruction observed in inflammatory joint disease.
Migita
K
K
First Department of Internal Medicine Nagasaki University School of Medicine, Japan. eguchi@net.nagasaki-u. ac. jp
Eguchi
K
K
Kawabe
Y
Y
Ichinose
Y
Y
Tsukada
T
T
Origuchi
T
T
Aoyagi
T
T
Nagataki
S
S
D001172:Arthritis, Rheumatoid / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D004306:Dose-Response Relationship, Immunologic; D004768:Enterotoxins / Q000276:immunology*; D004790:Enzyme Induction; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000502:physiology; D019278:Matrix Metalloproteinase 3 / Q000096:biosynthesis*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D018089:Superantigens / Q000276:immunology*; D013583:Synovial Membrane / Q000201:enzymology* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
D004768:Enterotoxins; D007375:Interleukin-1; D011500:Protein Synthesis Inhibitors; D018089:Superantigens; D014409:Tumor Necrosis Factor-alpha; C026066:enterotoxin A, Staphylococcal; D007371:Interferon-gamma; D003513:Cycloheximide; D019278:Matrix Metalloproteinase 3