Mechanism of action of TNF-alpha-stimulated prostaglandin production in cultured bovine luteal cells.
Tumor necrosis factor-alpha (TNF-alpha) influences hormone synthesis of many ovarian cell types and can also exert cytotoxic effects, possibly by increasing the synthesis of prostaglandins. The purpose of the present study was to characterize the mechanism of TNF-alpha-stimulated prostaglandin; F2 alpha (PGF2 alpha) production in cultured bovine luteal cells. Inhibitors of RNA and protein synthesis (actinomycin D and cycloheximide, respectively) completely blocked TNF-alpha-stimulated PGF2 alpha production. The phospholipase A2 inhibitor, aristolochic acid, prevented TNF-alpha-stimulated, but not basal, PGF2 alpha production, whereas the phospholipase C inhibitor, compound 48/80, was without effect. The addition of arachidonic acid to cultures did not overcome the inhibitory effects of cycloheximide or aristolochic acid. In conclusion, TNF-alpha-stimulated prostaglandin production by bovine luteal cells is dependent upon the stimulation of phospholipase A2 through mechanisms which require synthesis of RNA and protein.
Townson
D H
DH
Department of Animal Sciences, Ohio State University, Columbus 43210 USA.
Pate
J L
JL
D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology; D034341:Aristolochic Acids; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003338:Corpus Luteum / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D015237:Dinoprost / Q000096:biosynthesis*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D010616:Phenanthrenes / Q000494:pharmacology; D010741:Phospholipases A / Q000037:antagonists & inhibitors; D054467:Phospholipases A2; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors
D034341:Aristolochic Acids; D004791:Enzyme Inhibitors; D010616:Phenanthrenes; D011500:Protein Synthesis Inhibitors; D014409:Tumor Necrosis Factor-alpha; D003609:Dactinomycin; D016718:Arachidonic Acid; C000228:aristolochic acid I; D003513:Cycloheximide; D015237:Dinoprost; D010741:Phospholipases A; D054467:Phospholipases A2; D010738:Type C Phospholipases