Interferon-τ Blocks the Stimulatory Effect of Tumor Necrosis Factor-α on Prostaglandin F_2α Synthesis by Bovine Endometrial Stromal Cells

Tumor necrosis factor-α (TNFα) has been shown to be a potent stimulator of prostaglandin (PG) F_2α synthesis in bovine endometrial stromal cells. The aims of the present study were to determine the effect of interferon-τ (IFNτ) on TNFα-stimulated PGF _2α synthesis and the intracellular mechanisms of TNFα and IFNτ action in the stromal cells. When cultured bovine stromal cells were exposed to TNFα (0.006-0.6 nM) for 24 h, the production of PGF _2α and cyclooxygenase (COX)-2 gene expression were stimulated by TNFα (0.06-0.6 nM, P < 0.05). Moreover, a specific COX-2 inhibitor (NS-398; 5 nM) blocked the stimulatory effect of TNFα on PGF _2α production (P < 0.05). Although IFNτ (0.03-30 ng/ml) did not stimulate basal PGF_2α production in the stromal cells, it suppressed TNFα action in PGF_2α production dose dependently (P < 0.05). Moreover, the stimulatory effect of TNFα (0.6 nM) on COX-2 gene expression was completely blocked by IFNτ (30 ng/ml; P < 0.05), although the gene expression of COX-2 was not influenced by IFNτ. The overall results indicate that the stimulatory effect of TNFα on PGF_2α. production is mediated by the up-regulation of COX-2 gene expression and suggest that one of the mechanisms of the inhibitory effect of IFNτ on luteolysis is the inhibition of TNFα action in PGF_2α production in the stromal cells by the down-regulation of COX-2 gene expression stimulated by TNFα.