The expression of STAT3 inhibited the NF-ΚB signalling pathway and reduced inflammatory responses in mice with viral myocarditis

Background: The aim of this study was to investigate the mechanism of STAT3 in reducing the inflammatory responses in mice with viral myocarditis (VMC). Methods: Induce and generate viral myocarditis by using coxsackievirus B3 (CVB3) infected cardiomyocytespecific STAT3 conditional knockout (STAT3cKO) mice and BALB/c mice. Use RT-PCR and western blot techniques to detect the expression of related cytokines in the uninfected wild-type mice group (Control group), myocarditis wild-type mice group (Model group) and STAT3cKO group, as well as the differentiation of spleen T cells in each group. Eukaryotic expression plasmid pcDNA3-STAT3 can reduce the expression of inflammatory factors the in vitro cultured cardiomyocytes of the STAT3cKO group. Results: RT-PCR showed that compared with the Control group, the expression levels of VMC-related genes (NF kappa B, TNF-alpha, IL-1 beta and IL-1) and anti-inflammation-related cytokines (IL-10 and TGF-beta) in the Model group went up (*p < 0.05, **p < 0.01, ***p < 0.001); and also compared with the Control group, the rise in the expression levels of the above VMC-related genes in the STAT3cKO group was particularly significant (***p < 0.001, ****p < 0.0001) but there was no significant difference in the expression of IL-10 and TGF-beta. After 4 weeks, a second RT-PCR showed that the expression of inflammation-related genes in the STAT3cKO group continued to be activated (***p < 0.001, ****p < 0.0001). Western blotting was performed to detect the expression of p65, a key protein of the NF-kappa B signalling pathway. The results showed that the p65 protein content was increased and the IL-10 protein content was decreased in the STAT3cKO group; the results of the T cell differentiation test showed that the T cell differentiation rate increased in the STAT3cKO group (**p < 0.01). Eukaryotic expression plasmid pcDNA3-STAT3 could reduce the expression of NF-kappa B, TNF-alpha, IL-1 beta and IL-17 (**p < 0.01). Conclusion: The expression of STAT3 gene in VMC could to a certain extent inhibit the NF-kappa B signalling pathway and reduce the inflammatory responses of VMC.

Automated summary

This study demonstrates that the STAT3 gene can inhibit the NF-kappa B signaling pathway to reduce the inflammatory responses in viral myocarditis to a certain extent.