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  2. 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

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

  • Eur J Pharmacol. 2021 Jun 5;900:174067. doi: 10.1016/j.ejphar.2021.174067.
He Peng-Fei 1 A-Ru-Na 2 Chen Hui 2 Wei Hong-Yu 2 Cao Jin-Shan 2
Affiliations

Affiliations

  • 1 College of Veterinary Medicine, Inner Mongolia Agricultural University, Hohhot, 010018, PR China. Electronic address: hppfy@126.com.
  • 2 College of Veterinary Medicine, Inner Mongolia Agricultural University, Hohhot, 010018, PR China.
Abstract

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. α7 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 anti-inflammatory effects and mechanism of α7-nACh receptor on LPS-induced inflammation in bovine endometrial tissues cultured in vitro. The results suggested that activation of α7-nACh receptor significantly suppressed the mRNA expression levels of interleukin 1β (IL-1β), IL-6, IL-8, and tumor necrosis factor alpha (TNF-α) in bovine endometrial tissues. Western blot and enzyme-linked immunosorbent assay (ELISA) detection results showed that activation of α7-nACh receptor inhibited LPS-induced phosphorylation of Janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3). Moreover, α7-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 α7-nACh receptor increased COX-2 expression and PGE2 production, compared with COX-2 Inhibitor treatment. In conclusion, activation of the cholinergic system through α7-nACh receptor agonist has suppressed inflammation of bovine endometrial tissues via JAK2/STAT3 pathway and potential COX-2-derived PGE2.

Keywords

Bovine endometritis; COX-2; JAK2/STAT3 pathway; PGE(2); alpha7 nicotinic acetylcholine receptor.

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