Protective Role of the Cholinergic Anti-Inflammatory Pathway in a Mouse Model of Viral Myocarditis

作者：Zheng Cheng; Ge Li Sha; Zhao Jing Lin; Zhang Wen Wu; Chen Xue Si; Chen Xing Xing; Li Yue Chun^*

来源：PLos One, 2014, 9(11): e112719.

DOI：10.1371/journal.pone.0112719

Background: Activation of the cholinergic anti-inflammatory pathway, which relies on the alpha 7nAchR (alpha 7 nicotinic acetylcholine receptor), has been shown to decrease proinflammatory cytokines. This relieves inflammatory responses and improves the prognosis of patients with experimental sepsis, endotoxemia, ischemia/reperfusion injury, hemorrhagic shock, pancreatitis, arthritis and other inflammatory syndromes. However, whether the cholinergic anti-inflammatory pathway has an effect on acute viral myocarditis has not been investigated. Here, we studied the effects of the cholinergic anti-inflammatory pathway on acute viral myocarditis.
Methodology/Principal Findings: In a coxsackievirus B3 murine myocarditis model (Balb/c), nicotine and methyllycaconitine were used to stimulate and block the cholinergic anti-inflammatory pathway, respectively. Relevant signal pathways were studied to compare their effects on myocarditis, survival rate, histopathological changes, ultrastructural changes, and cytokine levels. Nicotine treatments significantly improved survival rate, attenuated myocardial lesions, and downregulated the expression of TNF-alpha and IL-6. Methyllycaconitine decreased survival rate, aggravated myocardial lesions, and upregulated the expression of TNF-alpha and IL-6. In addition, levels of the signaling protein phosphorylated STAT3 were higher in the nicotine group and lower in the methyllycaconitine group compared with the untreated myocarditis group.
Conclusions/Significance: These results show that nicotine protects mice from CVB3-induced viral myocarditis and that methyllycaconitine aggravates viral myocarditis in mice. Because nicotine is a alpha 7nAchR agonist and methyllycaconitine is a alpha 7nAchR antagonist, we conclude that alpha 7nAchR activation increases the phosphorylation of STAT3, reduces the expression of TNF-alpha and IL-6, and, ultimately, alleviates viral myocarditis. We also conclude that blocking alpha 7nAchR reduces the phosphorylation of STAT3, increases the expression of TNF-alpha and IL-6, aggravating viral myocarditis.

• 出版日期2014-11-14
• 单位温州医科大学