Docosahexaenoic Acid (DHA) Decreases IL-6 and Prostaglandin-Endoperoxide Synthase 2 mRNA Expression and IL-6 Protein Release, While Increasing Resolvin D1 and CXCL8 mRNA Expression and Protein Release in BovineEndometrial Cells

The endometrial immune response in postpartum cows is key to maintaining uterine health and preventing inflammatory diseases such as metritis and endometritis. Appropriate management strategies and diets that enhance the immune response are crucial during the transition period; therefore, diets rich in omega-3 fatty acids have been proposed for their potential beneficial effects on cows. Docosahexaenoic acid (DHA) is an omega-3 fatty acid with anti-inflammatory effects in immune cells; however, its effects on bovine endometrial immunity are not fully known. This study aimed to determine the effect of DHA on the inflammatory response in bovine endometrial (BEND) cells. BEND cells were incubated with DHA without or with lipopolysaccharide (LPS), and the mRNA expressions of prostaglandin-endoperoxide synthase 2 (PTGS2), interleukin (IL)-6, and CXCL8 were analyzed using RT-qPCR. The protein amount of IL-6, or CXCL8, and Resolvin D1 (RvD1) in the cell culture medium were analyzed using ELISA. DHA significantly reduced the expression of LPS-induced IL-6 and PTGS2 but increased LPS-induced CXCL8 expression. In addition, DHA reduced LPS-induced ERK1/2 and Akt phosphorylation, as assessed by immunoblotting. DHA increased the production of RvD1, a metabolite of DHA, at 8 and 24 h. In addition, RvD1 reduced LPS-induced CXCL8 production and increased the phosphorylation of ERK1/2 and Akt. Finally, changes in metabolite levels, such as an increase in 2-hydroxypyridine in DHA-treated cells, were obtained using a metabolomic assay. In conclusion, DHA reduced IL-6 and PTGS2 mRNA expression and IL-6 protein release and increased RvD1 levels in bovine endometrial cells, which suggest that DHA could have beneficial effects on endometrial immunity. The increase in CXCL8 mRNA expression and protein release induced by DHA remains to be studied; however, it could play a role in the innate defensive mechanisms of phagocytes.