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1 July 2004 Interferon-τ Induces Degradation of Prostaglandin H Synthase-2 Messenger RNA in Bovine Endometrial Cells Through a Transcription-Dependent Mechanism
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Abstract

A series of experiments were undertaken to examine the effects of interferon (IFN)-τ on regulation of prostaglandin H synthase (PGHS)-2 mRNA in bovine endometrial (BEND) cells as a means to elucidate the actions of IFN-τ to maintain pregnancy. The objective was to determine if IFN-τ 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 μg/ml) or the p38 mitogen-activated protein kinase (MAPK) inhibitor, SB203580 (1 μM), were added at 3 h, followed by addition of IFN-τ (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 μM) decreased PGHS-2 mRNA. Addition of IFN-τ (50 ng/ml) reduced PGHS-2 mRNA, which was not observed when actinomycin D was present. Concurrent treatments of cells with SB203580 and IFN-τ (5 ng/ml) decreased concentrations of PGHS-2 mRNA in an additive manner. Although IFN-τ reduced PGHS-2 mRNA concentrations, phosphorylation of p38 MAPK was induced by IFN-τ, PdBu, and PdBu combined with IFN-τ after 10 min of treatment. Both the p38 MAPK inhibitor and IFN-τ decreased prostaglandin F 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 in BEND cells. Interferon-τ mediates a transcription-dependent mechanism, which induces degradation of PGHS-2 mRNA. However, the consequences of an IFN-τ-induced activation of p38 MAPK warrant further investigation, because inhibition of p38 MAPK caused a degradation of PGHS-2 mRNA.

Aydin Guzeloglu, Prem Subramaniam, Frank Michel, and William W. Thatcher "Interferon-τ Induces Degradation of Prostaglandin H Synthase-2 Messenger RNA in Bovine Endometrial Cells Through a Transcription-Dependent Mechanism," Biology of Reproduction 71(1), 170-176, (1 July 2004). https://doi.org/10.1095/biolreprod.103.025411
Received: 12 November 2003; Accepted: 1 February 2004; Published: 1 July 2004
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