title: Interleukin-17A contributes to myocardial ischemia/reperfusion injury by regulating cardiomyocyte apoptosis and neutrophil infiltration.
abstract: OBJECTIVE
  This study tested whether interleukin (IL)-17A is involved in the pathogenesis of mouse myocardial ischemia/reperfusion (I/R) injury and investigated the mechanisms.
  
  
  BACKGROUND
  Inflammatory processes play a major role in myocardial I/R injury. We recently identified IL-17A as an important cytokine in inflammatory cardiovascular diseases such as atherosclerosis and viral myocarditis. However, its role in myocardial I/R injury remains unknown.
  
  
  METHODS
  The involvement of IL-17A was assessed in functional assays in mouse myocardial I/R injury by neutralization/repletion or genetic deficiency of IL-17A, and its mechanism on cardiomyocyte apoptosis and neutrophil infiltration were further studied in vivo and in vitro.
  
  
  RESULTS
  Interleukin-17A was elevated after murine left coronary artery ligation and reperfusion. Intracellular cytokine staining revealed that γδT lymphocytes but not CD4(+) helper T cells were a major source of IL-17A. Anti-IL-17A monoclonal antibody treatment or IL-17A knockout markedly ameliorated I/R injury, as demonstrated by reduced infarct size, reduced cardiac troponin T levels, and improved cardiac function. This improvement was associated with a reduction in cardiomyocyte apoptosis and neutrophil infiltration. In contrast, repletion of exogenous IL-17A induced the opposite effect. In vitro study showed that IL-17A mediated cardiomyocyte apoptosis through regulating the Bax/Bcl-2 ratio, induced CXC chemokine-mediated neutrophil migration and promoted neutrophil-endothelial cell adherence through induction of endothelial cell E-selectin and inter-cellular adhesion molecule-1 expression.
  
  
  CONCLUSIONS
  IL-17A mainly produced by γδT cells plays a pathogenic role in myocardial I/R injury by inducing cardiomyocyte apoptosis and neutrophil infiltration.
authors.affiliation: Institute of Cardiology, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Yu-Hua
authors.initials: YH
authors.lastname: Liao
authors.forename: Ni
authors.initials: N
authors.lastname: Xia
authors.forename: Su-Feng
authors.initials: SF
authors.lastname: Zhou
authors.forename: Ting-Ting
authors.initials: TT
authors.lastname: Tang
authors.forename: Xin-Xin
authors.initials: XX
authors.lastname: Yan
authors.forename: Bing-Jie
authors.initials: BJ
authors.lastname: Lv
authors.forename: Shao-Fang
authors.initials: SF
authors.lastname: Nie
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Iwakura
authors.forename: Hong
authors.initials: H
authors.lastname: Xiao
authors.forename: Jing
authors.initials: J
authors.lastname: Yuan
authors.forename: Harish
authors.initials: H
authors.lastname: Jevallee
authors.forename: Fen
authors.initials: F
authors.lastname: Wei
authors.forename: Guo-Ping
authors.initials: GP
authors.lastname: Shi
authors.forename: Xiang
authors.initials: X
authors.lastname: Cheng
mesh_terms: D000818:Animals; D017209:Apoptosis; D002448:Cell Adhesion; D019743:Chemokines, CXC / Q000378:metabolism; D019040:E-Selectin / Q000378:metabolism; D042783:Endothelial Cells / Q000502:physiology; D055786:Gene Knockout Techniques; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D020381:Interleukin-17 / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D015428:Myocardial Reperfusion Injury / Q000276:immunology / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000502:physiology; D020556:Neutrophil Infiltration; D018384:Oxidative Stress; D016176:T-Lymphocyte Subsets / Q000378:metabolism*
chemical_list: D019743:Chemokines, CXC; D019040:E-Selectin; C090509:Icam1 protein, mouse; C098680:Il17a protein, mouse; D020381:Interleukin-17; D018799:Intercellular Adhesion Molecule-1