Fas-mediated stimulation induces IL-8 secretion by rheumatoid arthritis synoviocytes independently of CPP32-mediated apoptosis.
In this study, we investigated the IL-1 beta converting enzyme (ICE) family cysteine proteases responsible for the Fas-mediated apoptosis of rheumatoid arthritis (RA) synoviocytes and their involvement in proinflammatory cytokine production. CPP32 inhibitor, but not ICE inhibitor, was capable of inhibiting the Fas-mediated apoptosis of RA synovial cells. CPP32, but not ICE, was activated in response to anti-Fas stimulation. IL-8, but not IL-1 beta, was secreted from the anti-Fas-stimulated RA synoviocytes even in the presence of CPP32 inhibitor. These results demonstrated that CPP32, but not ICE, is the predominant cysteine protease that mediates the Fas-mediated apoptosis of RA synovial cells. We also demonstrated that anti-Fas stimulation of RA synoviocytes leads to IL-8 secretion independently of the CPP32-mediated apoptosis, which would accelerate inflammation.
Department of Immunology, Juntendo University School of Medicine, Tokyo, Japan.
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Sekine
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Yagita
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Kobata
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Hasunuma
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Nishioka
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Okumura
D017209:Apoptosis; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000473:pathology; D020170:Caspase 1; D053148:Caspase 3; D020169:Caspases; D002478:Cells, Cultured; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism*; D009842:Oligopeptides / Q000494:pharmacology; D013583:Synovial Membrane / Q000276:immunology* / Q000473:pathology; D019014:fas Receptor / Q000276:immunology / Q000502:physiology*
D015853:Cysteine Proteinase Inhibitors; D007375:Interleukin-1; D016209:Interleukin-8; D009842:Oligopeptides; C099158:acetyl-aspartyl-glutamyl-valyl-aspartal; D019014:fas Receptor; C096429:L 709049; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D003546:Cysteine Endopeptidases; D020170:Caspase 1