Article Text

PDF

Experimental research
Involvement of the STAT3-Th17 axis in viral myocarditis induced by Coxsackievirus B3
  1. Yan Yuluan,
  2. Yan Yuluan,
  3. Pang Yu,
  4. Wu Weifeng,
  5. Yang Fan,
  6. Kong Qing,
  7. Huang Yanlan
  1. The First Affiliated Hospital Of Guangxi Medical University, Guangxi, China

Abstract

Objective This study was designed to explore whether the STAT3-Th17 axis is involved in the pathology of viral myocarditis (VMC) induced by Coxsackievirus B3 (CVB3).

Methods We induced VMC with male BALB/c mice by CVB3 intraperitoneal injection (n=48), mice intraperitoneal with phosphate-buffered solution (PBS) were taken as controls (n=30). STAT3 mRNA expression in the myocardium of mice was assessed by semi-quantitative RT-PCR. Phosphorylated-STAT3 (p-STAT3) protein expression in the myocardium and spleens was evaluated by Western-blot. Splenic CD4+T cells of VMC mice were isolated by immunomagnetic beads and cultured in vitro for 48 h with S3I-201(a selective STAT3 inhibitor), p-STAT3 protein expression, the percentages of Th17 cells, IL-17 mRNA expression, IL-17 protein level in supernatants in the cultured CD4+T cells were detected by Western-blot, flow cytometric analysis, semi-quantitative RT-PCR, enzyme-linked immunosorbent assay, respectively.

Results The expression of STAT3 mRNA in myocardium and p-STAT3 protein expression in myocardium and spleen tissues in VMC group increased significantly from 1 to 6 weeks after CVB3 injection, the highest levels were observed on the fourth week. The expression of p-STAT3 protein and Th17 cells proliferation in cultured CD4+ T cells were greatly inhibited by administration of S3I-201 (200 μM, 500 μM), correspondingly, IL-17 mRNA expression and IL-17 protein level in the supernatants decreased dramatically.

Conclusions The STAT3-Th17 axis is involved in the pathology of VMC induced by CVB3. Blocking the STAT3-Th17 axis by a selective STAT3 inhibitor S3I-201 may be a potential therapeutic target for VMC.

Statistics from Altmetric.com

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.