acetyl-aspartyl-glutamyl-valyl-aspartal and Arthritis--Rheumatoid

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.

Topics: Apoptosis; Arthritis, Rheumatoid; Caspase 1; Caspase 3; Caspases; Cells, Cultured; Cysteine Endopeptidases; Cysteine Proteinase Inhibitors; fas Receptor; Humans; Interleukin-1; Interleukin-8; Oligopeptides; Synovial Membrane