Tumor necrosis factor-alpha alters bovine luteal cell synthetic capacity and viability.

Abstract

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.

Intraluteal Release of Progesterone and Prostaglandins during PGF2.ALPHA.-Induced Luteolysis in Ewes: Local Effects of Tumor Necrosis Factor-.ALPHA..

“…In addition, recent observations suggest that cytokines including tumor necrosis factor-α (TNF-α) released from macrophages may influence the process of functional luteolysis [5]. However, most data on granulosa cells in vitro have described the inhibitory actions of TNF-α on steroidogenesis [6][7][8], while the data on luteal cells in vitro revealed little or no effect of TNF-α [5,9,10] on the progesuring luteolysis, immune cells, especially white blood cell series such as macrophages [1][2][3], D eosinophils [3,4] and T lymphocytes [2], have been observed within the corpus luteum (CL). The major role of the immune cells within the CL at this stage is most likely to be a phagocytosis of the CL terone (P) production.…”

“…The major role of the immune cells within the CL at this stage is most likely to be a phagocytosis of the CL terone (P) production. Therefore, the predominant action of cytokines on luteal cells may be to induce the release of prostaglandins (PG) rather than to suppress steroidogenesis [5]. Indeed, we have demonstrated that TNF-α slightly stimulated the release of P and PGF2α from the microenvironment within the CL at the mid-luteal stage when it was applied through a microdialysis system (MDS) that was implanted in the CL in cyclic ewes [11].…”

“…Indeed, we have demonstrated that TNF-α slightly stimulated the release of P and PGF2α from the microenvironment within the CL at the mid-luteal stage when it was applied through a microdialysis system (MDS) that was implanted in the CL in cyclic ewes [11]. Additionally, the idea was proposed that luteal PGF2α may interact with uterine or exogenous PGF2α as a local luteolysin during luteolysis in the cow [5].…”

Effects of TN F-.ALPHA. Injection into the Ovarian Parenchyma on Luteal Blood Vessels in Rabbits.

“…Bagavandoss et al have reported that the number of macrophages infiltrating into the corpus luteum increases during luteolysis in rabbits [18,19], and not only PGF2a but also several kinds of cytokines produced by immunocytes play a role as luteolytic factors [18][19][20][21][22]. Tumor necrosis factor (TNF)-o produced by activated macrophages was discovered by Carswell et al [23].…”

“…Tumor necrosis factor (TNF)-o produced by activated macrophages was discovered by Carswell et al [23]. It has been demonstrated that TNF-a derived from macrophages which infiltrated into the corpus luteum plays a role in luteolysis [19,22]. TNF-a has many biological effects in in vivo and in vitro studies.…”