Regulation of prostaglandin synthesis by interleukin-1 beta in cultured bovine luteal cells.
Prostaglandins produced within the CL may serve as local modulators of CL function. The present study was designed to characterize the cellular mechanisms by which the cytokine interleukin-1 beta (IL-1 beta) stimulates prostaglandin production in cultured luteal cells. Cycloheximide (CHX) and actinomycin D (Act D) did not affect basal, but completely inhibited IL-1 beta-stimulated prostaglandin F2 alpha (PGF2 alpha) production (p < 0.05). The phospholipase A2 (PLA2) inhibitor, aristolochic acid (PLA2X), and the phospholipase C (PLC) inhibitor, compound 48/80 (PLCX), suppressed IL-1 beta-stimulated (p < 0.05), but not basal, PGF2 alpha production. The addition of exogenous arachidonic acid (AA) restored the stimulatory effect of IL-1 beta in PLCX-treated, but not in PLA2X-treated, cells, suggesting that PLA2 is a key regulatory point of IL-1 beta action. Chronic exposure of the luteal cells to IL-1 beta resulted in stimulatory effects beyond that of increasing AA availability, presumably by up-regulation of prostaglandin endoperoxide (PGH) synthase. Chronic exposure of luteal cells to IL-1 beta also inhibited progesterone production, but this effect appeared to be independent of endogenous PGF2 alpha production. The ability of IL-1 beta to comprehensively stimulate luteal PGF2 alpha production while inhibiting luteal progesterone production is suggestive that IL-1 beta may facilitate regression of the CL.
Townson
D H
DH
Department of Dairy Science, Ohio State University, Columbus 43210.
Pate
J L
JL
D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology; D034341:Aristolochic Acids; D002417:Cattle / Q000378:metabolism*; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D015237:Dinoprost / Q000096:biosynthesis; D005260:Female; D007375:Interleukin-1 / Q000494:pharmacology*; D008184:Luteal Cells / Q000187:drug effects / Q000378:metabolism*; D010616:Phenanthrenes / Q000494:pharmacology; D010741:Phospholipases A / Q000037:antagonists & inhibitors; D054467:Phospholipases A2; D011374:Progesterone / Q000096:biosynthesis; D011453:Prostaglandins / Q000096:biosynthesis*; D011994:Recombinant Proteins / Q000494:pharmacology; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology
D034341:Aristolochic Acids; D007375:Interleukin-1; D010616:Phenanthrenes; D011453:Prostaglandins; D011994:Recombinant Proteins; D003609:Dactinomycin; D016718:Arachidonic Acid; D003189:p-Methoxy-N-methylphenethylamine; D011374:Progesterone; C000228:aristolochic acid I; D003513:Cycloheximide; D015237:Dinoprost; D010741:Phospholipases A; D054467:Phospholipases A2; D010738:Type C Phospholipases