Pancreatic-type phospholipase A2 induces group II phospholipase A2 expression and prostaglandin biosynthesis in rat mesangial cells.
The effect of pancreatic group I phospholipase A2 (PLA2-I) on receptor-mediated expression of arthritic group II phospholipase A2 (PLA2-II) and its correlation with prostaglandin E2 (PGE2) synthesis were examined in cultured rat mesangial cells. Scatchard analysis using 125I-PLA2-I revealed the existence of a single class of specific binding sites for PLA2-I in rat mesangial cells with an equilibrium dissociation constant (Kd) of 1.6 nM and a maximum binding capacity of 10.1 fmol/10(6) cells. The mammalian mature type of PLA2-I specifically recognized this binding site, whereas its inactive zymogen and mammalian PLA2-II showed much lower affinities. PLA2-I markedly increased PLA2-II mRNA levels as well as PLA2-II secretion from the cells in a time- and dose-dependent manner that was closely correlated with PGE2 production. Both PLA2-II expression and PGE2 synthesis were completely suppressed by pretreatment of the cells with actinomycin D, cycloheximide, or dexamethasone. These results strongly suggest that there may be crosstalk between PLA2-I and PLA2-II via the specific PLA2-I receptor that elicits PGE2 synthesis.
Kishino
J
J
Shionogi Research Laboratories, Shionogi & Company, Ltd., Osaka, Japan.
Ohara
O
O
Nomura
K
K
Kramer
R M
RM
Arita
H
H
D000818:Animals; D001514:Bee Venoms / Q000494:pharmacology; D001665:Binding Sites; D001667:Binding, Competitive; D002478:Cells, Cultured; D003600:Cytosol / Q000201:enzymology; D015232:Dinoprostone / Q000096:biosynthesis*; D004546:Elapid Venoms / Q000494:pharmacology; D015870:Gene Expression; D005920:Glomerular Mesangium / Q000201:enzymology / Q000378:metabolism*; D015151:Immunoblotting; D007527:Isoenzymes / Q000096:biosynthesis / Q000378:metabolism* / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D010179:Pancreas / Q000201:enzymology*; D010741:Phospholipases A / Q000096:biosynthesis / Q000378:metabolism* / Q000494:pharmacology*; D054467:Phospholipases A2; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013552:Swine
D001514:Bee Venoms; D004546:Elapid Venoms; D007527:Isoenzymes; D011451:Prostaglandin-Endoperoxide Synthases; D010741:Phospholipases A; D054467:Phospholipases A2; D015232:Dinoprostone