Selective induction of the secretion of cathepsins B and L by cytokines in synovial fibroblast-like cells.

Abstract

We have investigated the potent influence of some cytokines, tumour necrosis factor-alpha (TNF-alpha), platelet-derived growth factor (PDGF), basic fibroblast growth factor (bFGF) and interferon-gamma (IFN-gamma), on the secretion of cysteine proteinases (cathepsins B and L) by cultured synovial fibroblast-like cells from patients with rheumatoid arthritis (RA). After treatment of synovial fibroblast-like cells with cytokines, culture media were evaluated for cathepsins B and L by enzyme immunoassays, and for cathepsin B and L activities using the enzymatic substrates. Z-Phe-Arg-AMC and Z-Arg-Arg-AMC, and specific inhibitors. Treatment of synovial fibroblast-like cells with TNF-alpha or PDGF resulted in a marked increase in cathepsin B secretion. Moreover, after prolonged PDGF treatment, the amount of secreted cathepsin B returned to the low control level. In contrast, bFGF led to increased cathepsin L secretion. IFN-gamma induced both cathepsin B and L secretion. Our results show that cytokines induce a selective secretion of cathepsins B and L by synovial fibroblast-like cells. This selective effect of cytokines on the secretion of cysteine proteinases suggests that synovial fibroblast-like cell-mediated articular degradation is a highly regulated process.