Deoxycholic acid inhibits Staphylococcus aureus-induced endometritis through regulating TGR5/PKA/NF-κB signaling pathway.

Endometritis, a common gynecological disease, is the most common cause of infertility. As a natural metabolite of gut microbiota, deoxycholic acid (DCA) has been reported to have anti-inflammatory function. In the current study, the protective role of DCA on Staphylococcus aureus (S.aureus)-induced endometritis was tested. In vivo, DCA inhibited uterine histological change, MPO activity, endometrial barrier disruption, and inflammatory cytokine production induced by S.aureus. In vitro, DCA suppressed S.aureus-induced TNF-α and IL-1ß production in mouse endometrial epithelial cells (mEECs). Also, DCA markedly suppressed S.aureus-induced NF-κB activation. Takeda G protein-coupled receptor 5 (TGR5)is a critical bile acid membranereceptor that mainly regulated the cyclic AMP (cAMP)/protein kinase A (PKA)signaling pathway to inhibit NF-κB activation. We found DCA significantly increased TGR5 and PKA expression and S.aureus-induced inflammatory cytokine production and NF-κB activation were prevented by TGR5 inhibitor and PKA inhibitor. In conclusion, DCA protected S.aureus-induced endometritis by regulating TGR5/PKA/NF-κB signaling pathway.