Ethyl pyruvate attenuated coxsackievirus B3-induced acute viral myocarditis by suppression of HMGB1/RAGE/NF-ΚB pathway.

Ying Yu,Yong Yu,Hong Jiang,Ruizhen Chen,Guijian Liu,Ming Liu,Yangang Su,Yuxi Liu,Peng Yu

doi:10.1186/s40064-016-1857-6

Abstract

Inflammation plays important roles in the pathogenesis of coxsackievirus B3 (CVB3)-induced acute viral myocarditis (AVMC). Ethyl pyruvate (EP) has been shown to be an anti-inflammatory agent. High mobility group box 1 (HMGB1)/receptor for advanced glycation end product (RAGE)/nuclear factor (NF)-ΚB pathway has close relation with inflammatory responses. Here, we investigated the effects of EP on CVB3-induced AVMC and potential mechanisms. The mice with AVMC were treated with EP (40 or 80 mg/kg/day) from day 5 to day 7 post-infection. EP significantly decreased the mortality of mice with AVMC. H&E staining and immunohistochemistry for HMGB1 demonstrated less inflammatory lesions and fewer abnormal location of HMGB1 in the hearts of AVMC mice receiving EP. Immuoblot showed that EP significantly inhibited the levels of HMGB1, RAGE, phospho(p)-NF-ΚB and p-I-ΚBα, and raised I-ΚBα expression in the hearts of AVMC mice. Furthermore, real-time PCR and Elisa displayed decreased levels of HMGB1, TNF-α, IL-1β, IL-17 and increased levels of IL-10 in the hearts and serum of AVMC mice treated with EP. Our findings suggest that EP protects against CVB3-induced AVMC that is associated with inhibition of HMGB1/RAGE/NF-ΚB pathway.

Highlights

Enteroviruses such as coxsackievirus B3 (CVB3) have been demonstrated to be the common causes of acute viral myocarditis (AVMC), which is characterized by myocardial inflammation (Kindermann et al 2012; Corsten et al 2012)
Hematoxylin and eosin (H&E) staining demonstrated inflammatory lesions were completely absent from the 1st day to the 4th day after CVB3 injection, while inflammatory areas were increasingly increased from the 5th day to the 8th day after infection (P < 0.05; Fig. 1)
Ethyl pyruvate decreases the mortality of AVMC mice and reduces inflammatory lesions in the hearts of mice with AVMC To assess whether ethyl pyruvate treatment could improve AVMC, ethyl pyruvate at the dose of 40 or 80 mg/kg/day was administrated from the 5th day to the 7th day after CVB3 infection

Summary

Introduction

Enteroviruses such as coxsackievirus B3 (CVB3) have been demonstrated to be the common causes of acute viral myocarditis (AVMC), which is characterized by myocardial inflammation (Kindermann et al 2012; Corsten et al 2012). Substantial evidences have confirmed that the main anti-inflammatory mechanism of ethyl pyruvate is attributed to the inhibition of levels and secretion of high mobility group box 1 Yu et al SpringerPlus (2016) 5:215 et al 2013), which is an important pro-inflammatory cytokine in activation of inflammatory reaction. We evaluated whether ethyl pyruvate attenuated CVB3-induced AVMC via down-regulation of HMGB1/RAGE/NF-ΚB pathway. Our results demonstrated that ethyl pyruvate significantly decreased mortality and reduced myocardial inflammation, which was closely associated with inhibition of HMGB1/RAGE/ NF-ΚB pathway in a murine model of AVMC

Methods

Results

Discussion

Conclusion