TY - JOUR
T1 - Mechanism of action of TNF-α-stimulated prostaglandin production in cultured bovine luteal cells
AU - Townson, David H.
AU - Pate, Joy L.
N1 - Funding Information:
This work was supported by USDA Grant 92-37203-8037. Salaries were provided by State and Federal funds appropriated to the Ohio Agricul-
PY - 1996/11
Y1 - 1996/11
N2 - Tumor necrosis factor-alpha (TNF-α) 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-α-stimulated prostaglandin F(2α) (PGF(2α)) production in cultured bovine luteal cells. Inhibitors of RNA and protein synthesis (actinomycin D and cycloheximide, respectively) completely blocked TNF-α-stimulated PGF(2α) production. The phospholipase A2 inhibitor, aristolochic acid, prevented TNF-α-stimulated, but not basal, PGF(2α) 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-α-stimulated prostaglandin production by bovine luteal cells is dependent upon the stimulation of phospholipase A2 through mechanisms which require synthesis of RNA and protein.
AB - Tumor necrosis factor-alpha (TNF-α) 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-α-stimulated prostaglandin F(2α) (PGF(2α)) production in cultured bovine luteal cells. Inhibitors of RNA and protein synthesis (actinomycin D and cycloheximide, respectively) completely blocked TNF-α-stimulated PGF(2α) production. The phospholipase A2 inhibitor, aristolochic acid, prevented TNF-α-stimulated, but not basal, PGF(2α) 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-α-stimulated prostaglandin production by bovine luteal cells is dependent upon the stimulation of phospholipase A2 through mechanisms which require synthesis of RNA and protein.
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U2 - 10.1016/S0090-6980(96)00104-9
DO - 10.1016/S0090-6980(96)00104-9
M3 - Article
C2 - 8948504
AN - SCOPUS:0030296899
SN - 0090-6980
VL - 52
SP - 361
EP - 373
JO - Prostaglandins
JF - Prostaglandins
IS - 5
ER -