title: IFN-tau increases PGE2 production and COX-2 gene expression in the bovine endometrium in vitro.
abstract: Prostaglandins (PGs) are well known for their role in reproductive processes. At the time of pregnancy recognition, PGF2alpha is luteolytic and PGE2 may be antiluteolytic and luteotropic. During the preimplantation period, interferon-tau (IFN-tau) is produced by the conceptus and plays a crucial role in maternal recognition of pregnancy in domestic ruminants. We have demonstrated previously that recombinant bovine and ovine interferon-tau (rbIFN-tau and roIFN-tau) stimulate PGE2 production in epithelial cells, changing the primary PG produced by these cells from F2alpha to E2. In stromal cells, where PGE2 is the major PG produced, roIFN-tau induced an increase of both types of PGs. The aim of this paper is to identify the possible involvement of cyclooxygenases (COXs) in the modulation of PG production by trophoblastic interferons. Epithelial and stromal cells cultured in vitro were isolated from bovine endometrium and stimulated with increasing doses (1, 10 and 20 microg/ml) of roIFN-tau. PG levels in the culture media were measured by enzyme immunoassays (EIA) and total RNA was extracted from the cells. Northern blot analysis was performed to quantify cyclooxygenase COX-1 (constitutive), COX-2 (inducible) and phospholipase A2 (PLA2) messenger RNA (mRNA) production in response to treatment. The results indicate that roIFN-tau treatment did not affect COX-1 and PLA2 mRNA production in either cell type, whereas COX-2 expression was upregulated in both. The up-regulation of COX-2 transcript was greater in stromal than in epithelial cells. The increase in COX-2 mRNA levels was concurrent with increased production of PGE2 and PGF2alpha in stromal cells and principally PGE2 in epithelial cells. Furthermore, addition of indomethacin (1 microM) and a specific COX-2 inhibitor (NS-398, 1 microM) blocked the roIFN-tau-stimulation of PG production in both cell types. The mechanism whereby elevated COX-2 expression results in a selective increase of PGE2 in epithelial cells remains to be elucidated. In stromal cells, an increase in COX-2 mRNA levels may explain increased PG production. The overall effect of roIFN-tau in the two cell types is a net increase in PGE2 output.
authors.affiliation: Département d'Ontogénie et Reproduction, Centre de Recherches du Centre Hospitalier de l'Université Laval, Ste-Foy, Que., Canada.
authors.forename: E
authors.initials: E
authors.lastname: Asselin
authors.forename: D
authors.initials: D
authors.lastname: Lacroix
authors.forename: M A
authors.initials: MA
authors.lastname: Fortier
mesh_terms: D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000096:biosynthesis*; D004717:Endometrium / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D007370:Interferon Type I / Q000494:pharmacology*; D007527:Isoenzymes / Q000096:biosynthesis*; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000494:pharmacology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000494:pharmacology
chemical_list: D007370:Interferon Type I; D007527:Isoenzymes; D011257:Pregnancy Proteins; D012333:RNA, Messenger; D011994:Recombinant Proteins; C020947:interferon tau; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone