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Coxsackievirus B3 induces viral myocarditis by upregulating toll-like receptor 4 expression

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Abstract

In the present study, we investigated the potential pathogenesis of coxsackievirus B3 (CVB3)-induced viral myocarditis and the promising protective effect of silencing RNA (small interfering RNA, siRNA). One hundred and twenty mice were included in the study, and 30 mice were intraperitoneally inoculated with CVB3 to establish an acute viral myocarditis model. The survival rate was observed for the CVB3-infected mouse model (MOD), and myocardial injury was examined by HE (hematoxylin and eosin) staining assay. Real-time PCR (RT-PCR) and Western blot assay were selected to detect the toll-like receptor 4 (TLR4) expression in myocardial tissues. The TLR4 gene was silenced for the MOD mice, and the effects of this treatment were observed. The results indicate that the expression of TLR4 mRNA and the protein significantly and persistently increased during the progression of CVB3-induced myocarditis. The activities of cardiac enzymes including CK, LDH, AST, and CK-MB were also enhanced in CVB3-induced myocardial tissues. Interestingly, when the TLR4 gene was silenced, the CVB3-induced TLR4 production was significantly decreased and the severity of myocarditis was significantly lessened. In conclusion, CVB3 may induce viral myocarditis by upregulating toll-like receptor 4 expression. The viral myocarditis can be ameliorated by silencing the TLR4 gene in the CVB3 viral myocarditis model, which may be a feasible therapeutic method for treatment of viral myocarditis.

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Abbreviations

AST:

aspartate transaminase

CK:

creatine kinase

CK-MB:

creatine kinase isoenzyme

CVB3:

coxsackievirus B3

HE:

hematoxylin and eosin

LDH:

lactate dehydrogenase

RT-PCR:

real-time PCR

siRNA:

small interfering RNA

TCID50 :

50% tissue culture infectious dose

TLR4:

toll-like receptor 4

TLR4/NF-κB:

toll-like receptor 4/nuclear factor κB signal pathway

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Authors and Affiliations

  1. Department of Cardiovascular Medicine, First Hospital of Xi’an, Xi’an, 710002, China

    Zhao Zhao, Yan Lu, Wen-Jun Liu, Man-Li Cheng & Yu-Qiang Ji

  2. Department of Cardiovascular Medicine, Affiliated Hospital of Xi’an Medical University, Xi’an, 710077, China

    Tian-Zhi Cai

Authors
  1. Zhao Zhao
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  2. Tian-Zhi Cai
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  3. Yan Lu
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  4. Wen-Jun Liu
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  5. Man-Li Cheng
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  6. Yu-Qiang Ji
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Corresponding author

Correspondence to Yu-Qiang Ji.

Additional information

Published in Russian in Biokhimiya, 2015, Vol. 80, No. 4, pp. 534–543.

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Zhao, Z., Cai, TZ., Lu, Y. et al. Coxsackievirus B3 induces viral myocarditis by upregulating toll-like receptor 4 expression. Biochemistry Moscow 80, 455–462 (2015). https://doi.org/10.1134/S0006297915040094

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  • DOI: https://doi.org/10.1134/S0006297915040094

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