Interferon-(tau) Blocks the Stimulatory Effect of Tumor Necrosis Factor-(alpha) on Prostaglandin F2(alpha) Synthesis by Bovine Endometrial Stromal Cells

Tumor necrosis factor-(alpha)TNF(alpha) has been shown to be a potent stimulator of prostaglandin (PG) F2 (alpha) synthesis in bovine endometrial stromal cells. The aims of the present study were to determine the effect of interferon-(tau)) on TNF(alpha)-stimulated PGF2(alpha) synthesis and the intracellular mechanisms of TNF(alpha) and IFN(tau) action in the stromal cells. When cultured bovine stromal cells were exposed to TNF(alpha)(0.006–0.6 nM) for 24 h, the production of PGF2(alpha) and cyclooxygenase (COX)-2 gene expression were stimulated by TNF (alpha)(0.06–0.6 nM, P < 0.05). Moreover, a specific COX-2 inhibitor (NS-398; 5 nM) blocked the stimulatory effect of TNF(alpha) on PGF2(alpha) production (P < 0.05). Although IFN(tau) (0.03–30 ng/ml) did not stimulate basal PGF2(alpha) production in the stromal cells, it suppressed TNF(alpha) action in PGF2(alpha) production dose dependently (P < 0.05). Moreover, the stimulatory effect of TNF(alpha) (0.6 nM) on COX-2 gene expression was completely blocked by IFN(tau) (30 ng/ml; P < 0.05), although the gene expression of COX-2 was not influenced by IFN(tau). The overall results indicate that the stimulatory effect of TNF(alpha)on PGF2(alpha)on PGF2(alpha) production is mediated by the up-regulation of COX-2 production is mediated by the up-regulation of COX-2 gene expression and suggest that one of the mechanisms of the inhibitory effect of IFN(tau) on luteolysis is the inhibition of TNF (alpha)action in PGF2(alpha) production in the stromal cells by the down-regulation of COX-2 gene expression stimulated by TNF(alpha).