Anti-inflammatory effects of the prostaglandin D 2 /prostaglandin DP1 receptor and lipocalin-type prostaglandin D 2 synthase/prostaglandin D 2 pathways in bacteria-induced bovine endometrial tissue

Dairy cows often develop different degrees of endometritis after calving and this is attributed to pathogenic bacterial infections such as by Escherichia coli and Staphylococcus aureus . Infection of the bovine endometrium causes tissue damage and increases the expression of prostaglandin D 2 (PGD 2 ), which exerts anti-inflammatory effects on lung inflammation. However, the roles of PGD 2 and its DP1 receptor in endometritis in cows remain unclear. Here, we examined the anti-inflammatory roles of the lipocalin-type prostaglandin D 2 synthase (L-PGDS)/PGD 2 and DP1 receptor regulatory pathways in bovine endometritis. We evaluated the regulatory effects of PGD 2 on inflammation and tissue damage in E. coli - and S. aureus -infected bovine endometrial cells cultured in vitro. We found that the secretion of pro-inflammatory cytokines interleukin (IL)-6, IL-1β, and tumour necrosis factor (TNF)-α as well as expression of matrix metalloproteinase (MMP)-2, platelet-activating factor receptor (PAFR), and high mobility group box (HMGB)-1 were suppressed after DP1 receptor agonist treatment. In contrast, IL-6, IL-1β, and TNF-α release and MMP-2, PAFR, and HMGB-1 expression levels were increased after treatment of bovine endometrial tissue with DP1 receptor antagonists. DP1-induced anti-inflammatory effects were dependent on cellular signal transduction. The L-PGDS/PGD 2 pathway and DP1 receptor induced anti-inflammatory effects in bovine endometrium infected with S. aureus and E. coli by inhibiting the mitogen-activated protein kinase and nuclear factor-κB signalling pathways, thereby reducing tissue damage. Overall, our findings provide important insights into the pathophysiological roles of PGD 2 in bovine endometritis and establish a theoretical basis for applying prostaglandins or non-steroidal anti-inflammatory drugs for treating endometrial inflammatory infertility in bovines.