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 microg/ml) or the p38 mitogen-activated protein kinase (MAPK) inhibitor, SB203580 (1 microM), 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 microM) 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 F(2alpha) 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 F(2alpha) 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.
Department of Animal Sciences, University of Florida, Gainesville, FL 32611, USA.
Aydin
A
Guzeloglu
Prem
P
Subramaniam
Frank
F
Michel
William W
WW
Thatcher
D000818:Animals; D002417:Cattle; D051546:Cyclooxygenase 2; D015237:Dinoprost / Q000378:metabolism; D004357:Drug Synergism; D004717:Endometrium / Q000166:cytology / Q000201:enzymology* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D007093:Imidazoles / Q000494:pharmacology; D007370:Interferon Type I / Q000494:pharmacology*; D007527:Isoenzymes / Q000235:genetics*; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D011257:Pregnancy Proteins / Q000494:pharmacology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics*; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology; D014158:Transcription, Genetic / Q000502:physiology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology
D004791:Enzyme Inhibitors; D007093:Imidazoles; D007370:Interferon Type I; D007527:Isoenzymes; D011257:Pregnancy Proteins; D011725:Pyridines; D012333:RNA, Messenger; D011994:Recombinant Proteins; C020947:interferon tau; D015240:Phorbol 12,13-Dibutyrate; D015237:Dinoprost; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580