標題: Interleukin-17 enhances cardiac ventricular remodeling via activating MAPK pathway in ischemic heart failure
作者: Chang, Shih-Lin
Hsiao, Ya-Wen
Tsai, Yung-Nan
Lin, Shien-Fong
Liu, Shuen-Hsin
Lin, Yenn-Jiang
Lo, Li-Wei
Chung, Fa-Po
Chao, Tze-Fan
Hu, Yu-Feng
Tuan, Ta-Chuan
Liao, Nan
Hsieh, Yu-Cheng
Wu, Tsu-Juey
Higa, Satoshi
Chen, Shih-Ann
分子醫學與生物工程研究所
Institute of Molecular Medicine and Bioengineering
關鍵字: Ventricular arrhythmias;Inflammation;IL-17;MAPK
公開日期: 1-Sep-2018
摘要: Background: We aimed to investigate the impact of interleukin (IL)-17 on ventricular remodeling and the genesis of ventricular arrhythmia (VA) in an ischemic heart failure (HF) model. The expression of the proinflammatory cytokine IL-17 is upregulated during myocardial ischemia and plays a fundamental role in post-infarct inflammation. However, the influence of IL-17 on the genesis of VA has not yet been studied. Methods and results: The level of inflammation and Th17 cell (CD4(+)IL-17(+)) expression in the rabbit model of ischemic HF were studied by flow cytometry, quantitative polymerase chain reaction (qPCR), and enzyme-linked immunosorbent assay (ELISA). The effect of IL-17 on VA induction following acute and chronic administration of IL-17 was determined using electrophysiological techniques and optical mapping. The expression of IL-17 target genes and related cytokines and chemokines in vivo and in vitro were measured using qPCR, ELISA, and immunoblotting. Th17 cells were markedly increased in the ischemic HF rabbit model. IL-17 directly induced VA in vivo and in vitro in a dose-dependent manner. IL-17 decreased conduction velocity, lengthened action potential duration, and increased the slope of the left ventricle (LV) restitution curve. IL-17 treatment led to fibrosis, collagen production and apoptosis in the LV. Furthermore, increased IL-17 signaling activated mitogen-activated protein kinase and increased the expression of downstream target genes, IL-6, TNF, CCL20, and CXCL1. An anti IL -17 neutralizing antibody abolished the effects of IL-17. Conclusions: The expression of IL-17 and its downstream target genes may play fundamental roles in inducing VA in ischemic HF.
URI: http://dx.doi.org/10.1016/j.yjmcc.2018.08.005
http://hdl.handle.net/11536/148197
ISSN: 0022-2828
DOI: 10.1016/j.yjmcc.2018.08.005
期刊: JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
Volume: 122
起始頁: 69
結束頁: 79
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