IL-28A在柯萨奇病毒B3诱导的心肌炎中的抗病毒及心肌细胞保护作用。

Antiviral and myocyte protective effects of IL-28A in coxsackievirus B3-induced myocarditis.

作者信息

Wang Shihong, Huang Xingyuan, Zhang Jing, Huang Congxin

机构信息

Department of Pediatrics, Renmin Hospital of Wuhan University, Wuhan University, Hubei, PR China.

Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan University, Hubei, PR China.

出版信息

Braz J Infect Dis. 2015 Mar-Apr;19(2):132-40. doi: 10.1016/j.bjid.2014.10.007. Epub 2014 Dec 17.

DOI:10.1016/j.bjid.2014.10.007

PMID:25528576

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9478766/

Abstract

OBJECTIVE

This study aimed to investigate whether interleukin-28A (IL-28A) plays a role in murine myocarditis induced by coxsackievirus B3 (CVB3), and to explore its possible mechanism involved.

METHODS

Male BALB/c mice both infected and not infected by CVB3 were randomly divided into four groups (n=40), untreated or treated with different doses of IL-28A for 4 days, and then sacrificed on days 4 and 7 post-infection. The heart samples were collected for histopathologic examination. Cardiac viral load was determined by a plaque assay. Additionally, immunoblot analysis, TUNEL assay, and immunohistochemistry were performed to examine the expression of signal transducer, activator of transcription 1 and 2 (STAT1 and STAT2), CVB3-induced apoptosis and the expression of Bcl-2, BAX and Caspase-3.

RESULTS

Compared to uninfected mice, the CVB3 infected mice exhibited higher mortality rate (p<0.001), apparent inflammation and myocardial lesion (p<0.01), and higher cardiac viral load (p<0.01). After CVB3 infection, IL-28A treated mice presented no death (p<0.001), reduced inflammation and myocardial lesion (p<0.01), and lower viral load (p<0.01) compared to untreated mice. Besides, treatment with IL-28A markedly increased the expressions of STAT1 and STAT2, and inhibited CVB3-induced apoptosis in myocardial cells with increased ratio of Bcl-2/BAX.

CONCLUSION

The antiviral and myocyte protective effects of IL-28A in CVB3-induced myocarditis are regulated by STAT1 and STAT2.

摘要

目的

本研究旨在探讨白细胞介素-28A（IL-28A）在柯萨奇病毒B3（CVB3）诱导的小鼠心肌炎中是否发挥作用，并探讨其可能的作用机制。

方法

将感染和未感染CVB3的雄性BALB/c小鼠随机分为四组（n = 40），分别不进行处理或用不同剂量的IL-28A处理4天，然后在感染后第4天和第7天处死。收集心脏样本进行组织病理学检查。通过蚀斑试验测定心脏病毒载量。此外，进行免疫印迹分析、TUNEL试验和免疫组织化学，以检测信号转导子和转录激活子1和2（STAT1和STAT2）的表达、CVB3诱导的细胞凋亡以及Bcl-2、BAX和半胱天冬酶-3的表达。

结果

与未感染小鼠相比，感染CVB3的小鼠死亡率更高（p < 0.001），有明显的炎症和心肌损伤（p < 0.01），心脏病毒载量更高（p < 0.01）。CVB3感染后，与未处理的小鼠相比，IL-28A处理的小鼠无死亡（p < 0.001），炎症和心肌损伤减轻（p < 0.01），病毒载量更低（p < 0.01）。此外，IL-28A处理显著增加了STAT1和STAT2的表达，并抑制了CVB3诱导的心肌细胞凋亡，同时Bcl-2/BAX比值增加。