Interferon-(tau) Induces Degradation of Prostaglandin H Synthase-2 Messenger RNA in Bovine Endometrial Cells Through a Transcription-Dependent Mechanism

A series of experiments were undertaken to examine the effects of interferon (IFN)-(tau) on regulation of prostaglandin H synthase (PGHS)-2 mRNA in bovine endometrial (BEND) cells as a means to elucidate the actions of IFN-(tau) to maintain pregnancy. The objective was to determine if IFN-(tau) mediates posttranscriptional regulation of PGHS-2 mRNA. Cells were treated with phorbol 12,13-dibutyrate (PdBu) for 3 h to induce PGHS-2 mRNA expression. Actinomycin D (0 or 1 (mu)g/ml) or the p38 mitogen-activated protein kinase (MAPK) inhibitor, SB203580 (1 (mu)M), were added at 3 h, followed by addition of IFN-(tau) (0 or 50 ng/ml) at 3.5 h and extraction of RNA at 4.5 h. The concentrations of PGHS-2 mRNA were stable between 3 and 4.5 h regardless of actinomycin D. Simultaneous treatment of PdBu-treated cells with actinomycin D and SB203580 (1 (mu)M) decreased PGHS-2 mRNA. Addition of IFN-(tau) (50 ng/ml) reduced PGHS-2 mRNA, which was not observed when actinomycin D was present. Concurrent treatments of cells with SB203580 and IFN-(tau) (5 ng/ml) decreased concentrations of PGHS-2 mRNA in an additive manner. Although IFN-(tau) reduced PGHS-2 mRNA concentrations, phosphorylation of p38 MAPK was induced by IFN-(tau) , PdBu, and PdBu combined with IFN-(tau) after 10 min of treatment. Both the p38 MAPK inhibitor and IFN-(tau) decreased prostaglandin F2(alpha) secretion, and decreases were additive when the two were given together. In summary, activation of p38 MAPK by PdBu is required for continued presence of PGHS-2 mRNA and secretion of prostaglandin F2(alpha) in BEND cells. Interferon-(tau) mediates a transcription-dependent mechanism, which induces degradation of PGHS-2 mRNA. However, the consequences of an IFN-(tau)-induced activation of p38 MAPK warrant further investigation, because inhibition of p38 MAPK caused a degradation of PGHS-2 mRNA.