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.
Doualla-Bell
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Perinatal Research and Developmental Pharmacology Unit, Lady Davis Institute for Medical Research, Sir Mortimer B. Davis Jewish General Hospital, Montréal, Québec H3T 1E2, Canada. fdoualla@ldi.jgh.mcgill.ca
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D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism; D004789:Enzyme Activation / Q000502:physiology; D005260:Female; D007370:Interferon Type I / Q000494:pharmacology*; D050832:Interferon-Stimulated Gene Factor 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009215:Myometrium / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011257:Pregnancy Proteins / Q000494:pharmacology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011453:Prostaglandins / Q000096:biosynthesis; D050794:STAT1 Transcription Factor; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D015854:Up-Regulation; D048051:p38 Mitogen-Activated Protein Kinases
D004268:DNA-Binding Proteins; D007370:Interferon Type I; D050832:Interferon-Stimulated Gene Factor 3; D011257:Pregnancy Proteins; D011453:Prostaglandins; D050794:STAT1 Transcription Factor; D015534:Trans-Activators; D014157:Transcription Factors; C020947:interferon tau; D011451:Prostaglandin-Endoperoxide Synthases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases