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Protective role of the cholinergic anti-inflammatory pathway in a mouse model of viral myocarditis.

Cheng Z, Li-Sha G, Jing-Lin Z, Wen-Wu Z, Xue-Si C, Xing-Xing C, Yue-Chun L - PLoS ONE (2014)

Bottom Line: Nicotine treatments significantly improved survival rate, attenuated myocardial lesions, and downregulated the expression of TNF-α and IL-6.Because nicotine is a α7nAchR agonist and methyllycaconitine is a α7nAchR antagonist, we conclude that α7nAchR activation increases the phosphorylation of STAT3, reduces the expression of TNF-α and IL-6, and, ultimately, alleviates viral myocarditis.We also conclude that blocking α7nAchR reduces the phosphorylation of STAT3, increases the expression of TNF-α and IL-6, aggravating viral myocarditis.

View Article: PubMed Central - PubMed

Affiliation: Department of Cardiology, Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.

ABSTRACT

Background: Activation of the cholinergic anti-inflammatory pathway, which relies on the α7nAchR (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-α and IL-6. Methyllycaconitine decreased survival rate, aggravated myocardial lesions, and upregulated the expression of TNF-α 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 α7nAchR agonist and methyllycaconitine is a α7nAchR antagonist, we conclude that α7nAchR activation increases the phosphorylation of STAT3, reduces the expression of TNF-α and IL-6, and, ultimately, alleviates viral myocarditis. We also conclude that blocking α7nAchR reduces the phosphorylation of STAT3, increases the expression of TNF-α and IL-6, aggravating viral myocarditis.

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Related in: MedlinePlus

The effects of nicotine and methyllycaconitine on survival rate.The day of virus inoculation was defined as day 0, during the 14-day observation, there were no deaths happened in the control group. In the other three groups, the period from day 5th to 10th was demonstrated to be the death peak, the survival rate of the CVB3-inoculated was 45% for those treated with saline, 80% for those treated with nicotine, and 40.0% for those treated with methyllycaconitine. Compared to the myocarditis and methyllycaconitine groups, the survival rate was significantly higher in the nicotine group (P<0.05).
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pone-0112719-g001: The effects of nicotine and methyllycaconitine on survival rate.The day of virus inoculation was defined as day 0, during the 14-day observation, there were no deaths happened in the control group. In the other three groups, the period from day 5th to 10th was demonstrated to be the death peak, the survival rate of the CVB3-inoculated was 45% for those treated with saline, 80% for those treated with nicotine, and 40.0% for those treated with methyllycaconitine. Compared to the myocarditis and methyllycaconitine groups, the survival rate was significantly higher in the nicotine group (P<0.05).

Mentions: There were no deaths in the control group during the 14-day observation period. The survival rate of the CVB3-inoculated mice after 14 days was 45% for those treated with saline, 80% for those treated with nicotine, and 40.0% for those treated with methyllycaconitine. The day of virus inoculation was defined as day 0, and the period from day 5th to 10th was demonstrated to be the death peak. Compared to the myocarditis and methyllycaconitine groups, the survival rate was significantly higher in the nicotine group (Figure 1).


Protective role of the cholinergic anti-inflammatory pathway in a mouse model of viral myocarditis.

Cheng Z, Li-Sha G, Jing-Lin Z, Wen-Wu Z, Xue-Si C, Xing-Xing C, Yue-Chun L - PLoS ONE (2014)

The effects of nicotine and methyllycaconitine on survival rate.The day of virus inoculation was defined as day 0, during the 14-day observation, there were no deaths happened in the control group. In the other three groups, the period from day 5th to 10th was demonstrated to be the death peak, the survival rate of the CVB3-inoculated was 45% for those treated with saline, 80% for those treated with nicotine, and 40.0% for those treated with methyllycaconitine. Compared to the myocarditis and methyllycaconitine groups, the survival rate was significantly higher in the nicotine group (P<0.05).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4232511&req=5

pone-0112719-g001: The effects of nicotine and methyllycaconitine on survival rate.The day of virus inoculation was defined as day 0, during the 14-day observation, there were no deaths happened in the control group. In the other three groups, the period from day 5th to 10th was demonstrated to be the death peak, the survival rate of the CVB3-inoculated was 45% for those treated with saline, 80% for those treated with nicotine, and 40.0% for those treated with methyllycaconitine. Compared to the myocarditis and methyllycaconitine groups, the survival rate was significantly higher in the nicotine group (P<0.05).
Mentions: There were no deaths in the control group during the 14-day observation period. The survival rate of the CVB3-inoculated mice after 14 days was 45% for those treated with saline, 80% for those treated with nicotine, and 40.0% for those treated with methyllycaconitine. The day of virus inoculation was defined as day 0, and the period from day 5th to 10th was demonstrated to be the death peak. Compared to the myocarditis and methyllycaconitine groups, the survival rate was significantly higher in the nicotine group (Figure 1).

Bottom Line: Nicotine treatments significantly improved survival rate, attenuated myocardial lesions, and downregulated the expression of TNF-α and IL-6.Because nicotine is a α7nAchR agonist and methyllycaconitine is a α7nAchR antagonist, we conclude that α7nAchR activation increases the phosphorylation of STAT3, reduces the expression of TNF-α and IL-6, and, ultimately, alleviates viral myocarditis.We also conclude that blocking α7nAchR reduces the phosphorylation of STAT3, increases the expression of TNF-α and IL-6, aggravating viral myocarditis.

View Article: PubMed Central - PubMed

Affiliation: Department of Cardiology, Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.

ABSTRACT

Background: Activation of the cholinergic anti-inflammatory pathway, which relies on the α7nAchR (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-α and IL-6. Methyllycaconitine decreased survival rate, aggravated myocardial lesions, and upregulated the expression of TNF-α 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 α7nAchR agonist and methyllycaconitine is a α7nAchR antagonist, we conclude that α7nAchR activation increases the phosphorylation of STAT3, reduces the expression of TNF-α and IL-6, and, ultimately, alleviates viral myocarditis. We also conclude that blocking α7nAchR reduces the phosphorylation of STAT3, increases the expression of TNF-α and IL-6, aggravating viral myocarditis.

Show MeSH
Related in: MedlinePlus