Tumor necrosis factor-alpha alters bovine luteal cell synthetic capacity and viability.
Tumor necrosis factor-alpha (TNF-alpha) is a macrophage-derived cytokine that is also reportedly produced by granulosal cells and is localized in luteal cells. The present study employed serum-free culture of midcycle bovine luteal cells to investigate the effects of TNF-alpha, alone and with other cytokines, on luteal function. TNF-alpha (1-1000 ng/ml) produced a dose-dependent increase in prostaglandin (PG)F2 alpha and 6-keto-PGF1 alpha synthesis on all days of culture, but had no effect on basal progesterone (P4) production. TNF-alpha, in combination with other known stimulators of luteal PG synthesis, interleukin-1 beta (2.5 ng/ml) or interferon-gamma (IFN-gamma, 100 U/ml), had synergistic effects on PGF2 alpha production (greater than 50-fold above control, P less than 0.05) whereas interferon-alpha (1000 U/ml) significantly suppressed TNF-alpha-stimulated PGF2 alpha production. By day 7 of culture, TNF-alpha inhibited LH-stimulated P4 production (P less than 0.05). Luteal cell numbers were significantly reduced by IFN-gamma but not by TNF-alpha alone. However, the combination of TNF-alpha + IFN-gamma was extremely cytotoxic (only 20% of cells maintained as compared to control). Finally, TNF-alpha (100 ng/ml) enhanced the expression of Class I major histocompatibility complex antigens on cultured bovine luteal cells but did not alter IFN-gamma induction of Class II major histocompatibility complex antigens. In light of these findings, it appears that TNF-alpha, in conjunction with other cytokines, is a modulator of luteal cell function in vitro. The stimulation of PG synthesis, as well as cytotoxic effects of TNF-alpha, may suggest a role in luteolysis.
Benyo
D F
DF
Department of Dairy Science, Ohio State University, Columbus 43210.
Pate
J L
JL
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism*; D000818:Animals; D002417:Cattle; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003338:Corpus Luteum / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015237:Dinoprost / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D007700:Kinetics; D011374:Progesterone / Q000378:metabolism*; D011863:Radioimmunoassay; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D007375:Interleukin-1; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D011374:Progesterone; D015121:6-Ketoprostaglandin F1 alpha; D007371:Interferon-gamma; D015237:Dinoprost