Platelet-derived growth factor and fibroblast growth factor differentially regulate interleukin 1beta- and cAMP-induced group II phospholipase A2 expression in rat renal mesangial cells.
Expression of group II phospholipase A2 (PLA2; 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 1beta (IL-1beta) or tumor necrosis factor alpha and agents that elevate cellular levels of cyclic AMP (cAMP) such as forskolin, an activator of adenylate cyclase. Treatment of mesangial cells with IL-1beta or forskolin for 24 h induces group II PLA2 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-1beta- and forskolin-induced group II PLA2 activity. By Western and Northern blot analyses, we demonstrate that this is due to a reduction of PLA2 protein levels and the corresponding PLA2 mRNA steady-state levels. Basic fibroblast growth factor (bFGF) virtually does not inhibit IL-1beta-stimulated group II PLA2 activity, but markedly inhibits forskolin-induced expression of group II PLA2 activity. These effects are caused by changes in the corresponding PLA2 protein and PLA2 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-1beta-stimulated group II sPLA2 expression. In summary, our data suggest that PDGF and bFGF differentially modulate in a stimulus-specific manner the expression of group II PLA2 in mesangial cells.
Walker
G
G
Department of Pharmacology, Biozentrum, University of Basel, Klingelbergstr. 70, CH-4056 Basel, Switzerland.
Kunz
D
D
Pignat
W
W
Pfeilschifter
J
J
D000818:Animals; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D005920:Glomerular Mesangium / Q000187:drug effects* / Q000201:enzymology*; D007375:Interleukin-1 / Q000494:pharmacology; D010741:Phospholipases A / Q000096:biosynthesis* / Q000145:classification / Q000235:genetics*; D054467:Phospholipases A2; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction
D007375:Interleukin-1; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; D016222:Fibroblast Growth Factor 2; D005576:Colforsin; D000242:Cyclic AMP; D010741:Phospholipases A; D054467:Phospholipases A2