Platelet-derived growth factor and fibroblast growth factor differentially regulate interleukin 1 β- and cAMP-induced group II phospholipase A 2 expression in rat renal mesangial cells

Abstract

Expression of group II phospholipase A 2 (PLA 2; EC 3.1.1.4) in rat renal mesangial cells is triggered in response to two principal classes of activating signals. These two groups of activators comprise inflammatory cytokines such as interleukin 1 β (IL-1 β) or tumor necrosis factor α and agents that elevate cellular levels of cyclic AMP (cAMP) such as forskolin, an activator of adenylate cyclase. Treatment of mesangial cells with IL-1 β or forskolin for 24 h induces group II PLA 2 activity secreted into cell culture supernatants by about 15-fold and 11-fold, respectively. Platelet-derived growth factor (PDGF)-BB potently inhibits secretion of IL-1 β- and forskolin-induced group II PLA 2 activity. By Western and Northern blot analyses, we demonstrate that this is due to a reduction of PLA 2 protein levels and the corresponding PLA 2 mRNA steady-state levels. Basic fibroblast growth factor (bFGF) virtually does not inhibit IL-1 β-stimulated group II PLA 2 activity, but markedly inhibits forskolin-induced expression of group II PLA 2 activity. These effects are caused by changes in the corresponding PLA 2 protein and PLA 2 mRNA steady-state levels. Inhibition of protein kinase C (PKC) by the potent and selective PKC inhibitor calphostin C converted the inhibitory action of PDGF into a bFGF-type of response thus suggesting that PKC is a major effector in PDGF-induced inhibition of IL-1 β-stimulated group II sPLA 2 expression. In summary, our data suggest that PDGF and bFGF differentially modulate in a stimulus-specific manner the expression of group II PLA 2 in mesangial cells.