Tumor necrosis factor-α stimulates prostaglandin F2α secretion by bovine luteal cells via activation of mitogen-activated protein kinase and phospholipase A2 pathways

It has been well demonstrated that tumor necrosis factor-α (TNFα) stimulates prostaglandin (PG) F2α secretion by bovine corpus luteum (CL) in vitro. The objective of the present study was to clarify the intracellular signaling pathway of TNFα to stimulate PGF2α production in cultured bovine luteal cells. Bovine luteal cells that were obtained from mid-(days 8-12 after ovulation) CL were incubated with TNFα (0.6 nM) and/or various compounds as follows: U-73122 (an inhibitor of phospholipase [PL] C), ACA (an inhibitor of PL-A2), H-89 (an inhibitor of protein kinase [PK] A), calphostin C (an inhibitor of PK-C), L-NAME/L-NORG (inhibitors of nitric oxide synthase), and PD98059 (an inhibitor of mitogen-activated protein kinase [MAPK] kinase). Although U-73122 (0.1-10 μM), H-89 (0.1-10 μM), calphostin C (0.01-1 μM) and L-NAME/L-NORG (1-100 μM) did not affect TNFα-induced PGF2α secretion by the cultured cells, ACA (1-100 αM) and PD98059 (0.1-100 αM) inhibited TNFα-stimulated PGF2α secretion by the cells in a dose- dependent fashion (P < 0.05 or lower). These findings suggest that TNFα activates the MAPK and PL-A2 pathways in bovine luteal cells to stimulate PGF2α secretion. (C) 2000 Wiley-Liss, Inc.