Differential effects of interferon-τ on the prostaglandin synthetic pathway in bovine endometrial cells treated with phorbol ester

Abstract

Rationale for these experiments was to evaluate the dose effects of bovine interferon-τ (IFN-τ) on the prostaglandin secretory pathway of immortalized bovine endometrial (BEND) cells in response to phorbol 12, 13-dibutyrate (PdBu) and to characterize similar responses in primary bovine uterine epithelial cells as a biomonitor of embryo-induced antiluteolytic effects on the endometrium. The BEND cells were treated with PdBu (0 or 100 ng/mL) and IFN-τ (0 or 50 ng/mL) for 6 h. The PdBu stimulated secretions of PGF2α and prostaglandin E2 (PGE2). Co-treatment of cells with IFN-τ blocked PdBu-induced secretion of both PGF2α and PGE2. Treatment with PdBu for 6 h induced expression of prostaglandin H synthase-2 mRNA, prostaglandin H synthase-2 protein, and prostaglandin E synthase mRNA, which were blocked with concurrent addition of IFN-τ. Doses of IFN-τ (0.05, 0.5, 1, 5, 10, and 20 μg/ mL) were used with PdBu (0 and 100 ng/mL). The IFN-τ alone failed to stimulate secretion of PGF2a and PGE2, whereas IFN-τ doses <5 μg/mL suppressed PdBu-stimulated secretions of PGF 2α and PGE2. Uterine epithelial cells were isolated from cows at d 17 after estrus and were cultured to confluence in serum-free medium. Cells were treated with IFN-τ (0, 50, or 500 ng/mL) and PdBu (0 or 100 ng/mL) before media were collected after 24 h for PGF2α and PGE2 analyses. Treatment of primary uterine epithelial cells with PdBu induced PGF2α secretion, and IFN-τ (50 and 500 ng/mL) caused a reduction in PGF2α secretion induced by PdBu. In the absence of PdBu, IFN-τ increased basal secretion of PGF2α. Concentrations of PGE2 increased in response to PdBu, and the 50-ng/mL dose of IFN-τ had a stimulatory effect on PGE2 concentrations compared with the 500-ng/mL dose in the absence of PdBu. Phorbol ester-induced gene transcription as related to prostaglandin synthesis is regulated by IFN-τ in vitro.