title: Antiviral and myocyte protective effects of IL-28A in coxsackievirus B3-induced myocarditis.
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.
  
  
  CONCLUSIONS
  The antiviral and myocyte protective effects of IL-28A in CVB3-induced myocarditis are regulated by STAT1 and STAT2.
authors.affiliation: Department of Pediatrics, Renmin Hospital of Wuhan University, Wuhan University, Hubei, PR China.
authors.forename: Shihong
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Pediatrics, Renmin Hospital of Wuhan University, Wuhan University, Hubei, PR China.
authors.forename: Xingyuan
authors.initials: X
authors.lastname: Huang
authors.affiliation: Department of Pediatrics, Renmin Hospital of Wuhan University, Wuhan University, Hubei, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan University, Hubei, PR China. Electronic address: huangfornew@163.com.
authors.forename: Congxin
authors.initials: C
authors.lastname: Huang
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use*; D017209:Apoptosis; D053148:Caspase 3 / Q000276:immunology / Q000378:metabolism; D003384:Coxsackievirus Infections / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism; D015151:Immunoblotting; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007378:Interleukins / Q000276:immunology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009205:Myocarditis / Q000276:immunology / Q000378:metabolism / Q000821:virology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000276:immunology / Q000378:metabolism; D050794:STAT1 Transcription Factor / Q000276:immunology / Q000378:metabolism; D050795:STAT2 Transcription Factor / Q000276:immunology / Q000378:metabolism; D019562:Viral Load; D051028:bcl-2-Associated X Protein / Q000276:immunology / Q000378:metabolism; D000095022:Interferon Lambda
chemical_list: D000998:Antiviral Agents; D053148:Caspase 3; D007378:Interleukins; D019253:Proto-Oncogene Proteins c-bcl-2; D050794:STAT1 Transcription Factor; D050795:STAT2 Transcription Factor; D051028:bcl-2-Associated X Protein; C494826:BAX protein, human; C000595707:BCL2 protein, human; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C494079:STAT1 protein, human; C494084:STAT2 protein, human; C505407:CASP3 protein, human
keywords: Apoptosis; Coxsackievirus B3; IL-28A; Myocarditis