PMID- 8948504 OWN - NLM STAT- MEDLINE DCOM- 19970313 LR - 20190826 IS - 0090-6980 (Print) IS - 0090-6980 (Linking) VI - 52 IP - 5 DP - 1996 Nov TI - Mechanism of action of TNF-alpha-stimulated prostaglandin production in cultured bovine luteal cells. PG - 361-73 AB - 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. FAU - Townson, D H AU - Townson DH AD - Department of Animal Sciences, Ohio State University, Columbus 43210 USA. FAU - Pate, J L AU - Pate JL LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. PL - United States TA - Prostaglandins JT - Prostaglandins JID - 0320271 RN - 0 (Aristolochic Acids) RN - 0 (Enzyme Inhibitors) RN - 0 (Phenanthrenes) RN - 0 (Protein Synthesis Inhibitors) RN - 0 (Tumor Necrosis Factor-alpha) RN - 1CC1JFE158 (Dactinomycin) RN - 27YG812J1I (Arachidonic Acid) RN - 94218WFP5T (aristolochic acid I) RN - 98600C0908 (Cycloheximide) RN - B7IN85G1HY (Dinoprost) RN - EC 3.1.1.32 (Phospholipases A) RN - EC 3.1.1.4 (Phospholipases A2) RN - EC 3.1.4.- (Type C Phospholipases) SB - IM MH - Animals MH - Arachidonic Acid/pharmacology MH - *Aristolochic Acids MH - Cattle MH - Cell Division/drug effects MH - Cell Survival/drug effects MH - Cells, Cultured MH - Corpus Luteum/cytology/*drug effects/*metabolism MH - Cycloheximide/pharmacology MH - Dactinomycin/pharmacology MH - Dinoprost/*biosynthesis MH - Enzyme Inhibitors/pharmacology MH - Female MH - Phenanthrenes/pharmacology MH - Phospholipases A/antagonists & inhibitors MH - Phospholipases A2 MH - Protein Synthesis Inhibitors/pharmacology MH - Tumor Necrosis Factor-alpha/*pharmacology MH - Type C Phospholipases/antagonists & inhibitors EDAT- 1996/11/01 00:00 MHDA- 1996/11/01 00:01 CRDT- 1996/11/01 00:00 PHST- 1996/11/01 00:00 [pubmed] PHST- 1996/11/01 00:01 [medline] PHST- 1996/11/01 00:00 [entrez] AID - S0090698096001049 [pii] AID - 10.1016/s0090-6980(96)00104-9 [doi] PST - ppublish SO - Prostaglandins. 1996 Nov;52(5):361-73. doi: 10.1016/s0090-6980(96)00104-9.