A20 TNFAIP3 Alleviates CVB3-Induced Myocarditis via Inhibiting NF-κB SignalingReport as inadecuate




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Background

Viral myocarditis, which is most prevalently caused by Coxsackievirus B3 CVB3 infection, is a serious clinical condition characterized by cardiac inflammation. However, efficient therapies targeting inflammation are still lacking and much needed. A20, also known as tumor necrosis factor alpha induced protein 3 TNFAIP3 is a key negative regulator of inflammation. But whether A20 may affect cardiac inflammation during acute viral myocarditis remains to be elucidated. The aim of this study was to investigate the potential protective effect of A20 on CVB3-induced myocarditis.

Methodology-Principal Findings

Mice were intraperitoneally inoculated with CVB3 to establish acute viral myocarditis model. We found that the expression of pro-inflammatory cytokines, including tumor necrosis factor-α TNF-α, interleukin IL-1β, IL-6 and monocyte chemotactic protein-1 MCP-1 were markedly and persistently increased during the progression of CVB3-induced myocarditis, and positively correlated with the disease severity. Notably, intravenous injection in vivo with adenovirus expressed A20 Ad-A20 remarkably reduced CVB3-induced pro-inflammatory cytokines production and alleviated the severity of myocarditis. Further, we observed that nuclear factor-kappaB NF-κB signaling which mediates inflammatory response was significantly inhibited in CVB3-infected mice with Ad-A20 treatment. Finally, we revealed that A20 was required to inhibit CVB3-induced NF-κB signaling by restricting TNF receptor associated factor 6 TRAF6 ubiquitylation.

Conclusion-Significance

This study demonstrates the protective role of A20 against CVB3-induced myocarditis, which may provide a new therapeutic strategy for the treatment of viral myocarditis.



Author: Jun Gui, Yan Yue, Ruizhen Chen, Wei Xu, Sidong Xiong

Source: http://plos.srce.hr/



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