PDGF suppresses the activation of group II phospholipase A2 gene expression by interleukin 1 and forskolin in mesangial cells.
Treatment of rat mesangial cells with interleukin 1 beta (IL-1 beta) and forskolin greatly enhanced the expression of group II phospholipase A2 (PLA2) mRNA, with subsequent increased synthesis and secretion of PLA2, as detected by PLA2 activity measurements and immunoprecipitation of culture media of [35S]methionine-labelled mesangial cells. PDGF-BB dose-dependently suppressed the IL-1 beta- and forskolin-induced elevation of PLA2 mRNA, as well as PLA2 synthesis and secretion. In contrast, PDGF-AA had no inhibitory effect. The tyrosine kinase inhibitor genistein dose-dependently antagonized the inhibitory effect of PDGF-BB on IL-1 beta-stimulated PLA2 secretion, thus suggesting that tyrosine phosphorylation may be required for PDGF-BB inhibition of PLA2 gene expression in mesangial cells.
Research Department, Ciba-Geigy Ltd., Basel, Switzerland.
H
H
Mühl
T
T
Geiger
W
W
Pignat
F
F
Märki
H
H
van den Bosch
K
K
Vosbeck
J
J
Pfeilschifter
D000818:Animals; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D005920:Glomerular Mesangium / Q000187:drug effects / Q000201:enzymology*; D007375:Interleukin-1 / Q000494:pharmacology*; D010741:Phospholipases A / Q000037:antagonists & inhibitors* / Q000235:genetics; D054467:Phospholipases A2; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D051381:Rats
D007375:Interleukin-1; D010982:Platelet-Derived Growth Factor; D005576:Colforsin; D010741:Phospholipases A; D054467:Phospholipases A2