Effects Of EP₄ Receptor On Tissue Damage In Escherichia Coli-infected Endometrial Tissues Of Dairy Cows

Endometritis of dairy cows is a common disease caused by infections with bacteria in dairy cows after postnatal which seriously affect the reproductive capacity of dairy cows and the development of the dairy industry.The synthesis and secretion of prostaglandin E2(PGE2)is significantly increased in E.coli-infected dairy cows endometrial tissues and promote tissue damage and inflammation.PGE2 plays a biological role mainly through its corresponding receptors.However,this pro-inflammatory effect of PGE2 in E.coli-infected bovine endometrial tissues remains to be studied.In this study,EP4 receptor pathway was selected for experiment.The dairy cow endometrium tissues were cultured in vitro and infected with 1×106 cfu/mL of E.coli.And the E.coli-infected bovine endometrial tissues were treated with EP4 receptor agonist(CAY 10598),cyclooxygenase-2(COX-2)inhibitors(CAY10404 and NS398)and microsomal prostaglandin E synthase-1(mPGES-1)inhibitors(MF63 and MK886).The methods of real-time PCR,ELISA and Western Blot were used to examine the expression and secretion levels of COX-2,mPGES-1,pro-inflammatory factors(IL-1β,IL-6,IL-8,TNF-α)and two damage-associated molecular patterns(DAMPs),HMGB-1 and HABP1.The results show that EP4 receptor agonist and E.coli culture for 12 h significantly induced the expression and secretion of COX-2,mPGES-1,pro-inflammatory factors and DAMPs,and the endometrial epithelial cells and glandular cells of the cows disintegrate,which was attenuated by the addition of COX-2 or mPGES-1 inhibitors.These results indicate that EP4-COX-2/mPGES-1 can mediate the pathological accumulation and tissue damage of PGE2 in the endometrial tissues of cows infected with E.coli.