IFN-tau increases PGE(2) production and COX-2 gene expression in the bovine endometrium in vitro

[摘要] Prostaglandins (PGs) are well known for their role in reproductive processes. At the time of pregnancy recognition, PGF(2 alpha) is luteolytic and PGE(2) 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 PGE(2) production in epithelial cells, changing the primary PG produced by these cells from F-2 alpha to E-2. In stromal cells, where PGE(2) 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 mu g/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 A(2) (PLA(2)) messenger RNA (mRNA) production in response to treatment. The results indicate that roIFN-tau treatment did not affect COX-1 and PLA(2) 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 PGE(2) and PGF(2 alpha) in stromal cells and principally PGE(2) in epithelial cells. Furthermore, addition of indomethacin (1 mu M) and a specific COX-2 inhibitor (NS-398, 1 mu M) 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 PGE(2) 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 PGE(2) output. (C) 1997 Elsevier Science Ireland Ltd.

[发布日期] 1997-09-19

[关键词] epithelial and stromal cells;PGF(2 alpha);PGHS;cyclooxygenase;phospholipase;prostaglandin