Induction of PG G/H synthase-2 in bovine myometrial cells by interferon-tau requires the activation of the p38 MAPK pathway.

PGs are regulators of a plethora of uterine functions during reproductive processes, including uterine contractility. In bovine uterus, the rate-limiting step in PG synthesis is catalyzed by the PG endoperoxide G/H synthase (PGHS) enzymes. It has previously been established that PGHS-2 isoform expression is affected by the ruminant-specific interferon (IFN)-tau in bovine endometrial cells. Here, we show that PGHS-2 mRNA and protein levels are induced by IFN-tau in primary cell cultures from bovine myometrium. Treatment with recombinant bovine IFN-tau induces the activation of the JAK-STAT and p38 MAPK pathways in bovine myometrial cells. Inhibition of the p38 pathway by the specific inhibitor SB203580 strongly decreases PGHS-2 mRNA and protein expression without affecting the phosphorylation and DNA-binding of transcription factors STAT-1 and STAT-2. The p38 pathway regulates PGHS-2 expression at the posttranscriptional level, because the presence of SB203580 results in the destabilization of IFN-tau-induced PGHS-2 mRNA. Taken together, these data demonstrate the ability of IFN-tau to induce the activation of the JAK-STAT pathway in a manner similar to other types of IFN (i.e. alpha, beta, and gamma) and to regulate PGHS-2 mRNA stability through the activation of the p38 pathway. These findings provide new insights into the physiological function of IFN-tau, in regard to regulation of specific genes associated with myometrial contractility.