Activation of alpha7 nicotinic acetylcholine receptor protects bovine endometrial tissue against LPS-induced inflammatory injury via JAK2/STAT3 pathway and COX-2 derived prostaglandin E2

Bovine endometritis is one of the major postpartum diseases associated with infertility and subfertility, decreasing the benefit of dairy industry. It is important to develop alternate therapies for endometritis in the context of drug residues in the milk and hormone disorder in the estrous cycle. ?7 nicotine acetylcholine receptor has been identified as the core of ?cholinergic anti-inflammatory pathway (CAP)?, which is a potential drug target to inflammatory diseases. However, there has been still no study on its anti-inflammatory effects and mechanism on lipopolysaccharide (LPS)-induced bovine endometritis. This study aimed to demonstrate the underlying antiinflammatory effects and mechanism of ?7-nACh receptor on LPS-induced inflammation in bovine endometrial tissues cultured in vitro. The results suggested that activation of ?7-nACh receptor significantly suppressed the mRNA expression levels of interleukin 1? (IL-1?), IL-6, IL-8, and tumor necrosis factor alpha (TNF-?) in bovine endometrial tissues. Western blot and enzyme-linked immunosorbent assay (ELISA) detection results showed that activation of ?7-nACh receptor inhibited LPS-induced phosphorylation of Janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3). Moreover, ?7-nACh receptor agonist decreased the expression of cyclooxygenase 2 (COX-2) and microsomal prostaglandin E synthase-1(mPGES-1), as well as prostaglandin E2 (PGE2) secretion. Interestingly, in COX-2 inhibition experiment, activation of ?7-nACh receptor increased COX-2 expression and PGE2 production, compared with COX-2 inhibitor treatment. In conclusion, activation of the cholinergic system through ?7-nACh receptor agonist has suppressed inflammation of bovine endometrial tissues via JAK2/STAT3 pathway and potential COX-2-derived PGE2.

Automated summary

The study demonstrates that activation of the ?7-nACh receptor can significantly suppress mRNA expression levels of inflammatory factors in bovine endometrial tissues and inhibit LPS-induced inflammation through the JAK2/STAT3 pathway and potential COX-2-derived PGE2.