Promoting effects of IL‑23 on myocardial ischemia and reperfusion are associated with increased expression of IL‑17A and upregulation of the JAK2‑STAT3 signaling pathway

Liao,Yanxi; Hu,Xiaorong; Guo,Xin; Zhang,Bofang; Xu,Weipan; Jiang,Hong

doi:10.3892/mmr.2017.7771

Promoting effects of IL‑23 on myocardial ischemia and reperfusion are associated with increased expression of IL‑17A and upregulation of the JAK2‑STAT3 signaling pathway

Authors:
- Yanxi Liao
- Xiaorong Hu
- Xin Guo
- Bofang Zhang
- Weipan Xu
- Hong Jiang
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Affiliations: Department of Cardiology, Central Hospital of Wuhan, Wuhan, Hubei 430014, P.R. China, Department of Cardiology, Renmin Hospital of Wuhan University, Cardiovascular Research Institute of Wuhan University, Wuhan, Hubei 430060, P.R. China, Department of Cardiology, Huangshi Central Hospital, Affiliated Hospital of Hubei Polytechnic University, Edong Healthcare Group, Huangshi, Hubei 435002, P.R. China
Published online on: October 12, 2017 https://doi.org/10.3892/mmr.2017.7771
Pages: 9309-9316
Copyright: © Liao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Interleukin (IL)‑23, as a novel pro‑inflammatory cytokine, is important in several inflammatory diseases, including myocardial ischemia and reperfusion (I/R) injury, however, the underlying mechanism remains to be elucidated. The present study was designed to investigate the specific role of IL‑23 in myocardial I/R injury, and whether the Janus kinase 2/signal transducer and activator of transcription 3 (JAK2‑STAT3) signaling pathway, one of the important downstream signaling pathways of IL‑23, and the IL‑17A downstream pro‑inflammatory cytokine, were involved. Anesthetized rats underwent different treatments with adenovirus (Ad) vectors (Ad‑GFP, Ad‑IL‑23, Anti‑IL‑23 or Ad‑IL‑23+AG490) and were then subjected to ischemia for 30 min prior to 4 h reperfusion. The effects of the upregulation and downregulation of IL‑23 on myocardial injury, inflammatory responses in myocardial tissue, and myocardial apoptosis were measured accordingly. In addition, the levels of phosphorylated (P‑)JAK2 and P‑STAT3 were measured to assess the activity of the JAK2‑STAT3 signaling pathway. The results demonstrated that there was an increased expression of IL‑23 in the myocardial tissue exposed to myocardial I/R injury (P<0.05). The upregulation of IL‑23 significantly increased the infarct size and the expression levels of lactate dehydrogenase and creatine kinase (P<0.05). The upregulation of IL‑23 significantly increased inflammatory responses, as reflected by the high expression levels of IL‑17A, IL‑6, tumor necrosis factor‑α in the myocardial tissues (P<0.05). Furthermore, the upregulation of IL‑23 significantly facilitated the decrease in the B‑cell lymphoma 2 (Bcl‑2)/Bcl‑2‑associated X protein ratio, and the increases in the myocardial apoptotic index and expression of caspase‑3 induced by myocardial I/R (P<0.05). IL‑23 also activated the JAK2‑STAT3 signaling pathway, upregulating the expression levels of P‑JAK2 and P‑STAT3 in the myocardial tissues (P<0.05). Treatment with AG490, an inhibitor of JAK2‑STAT3, partially attenuated the pro‑inflammatory and pro‑apoptotic effects of IL‑23 (P<0.05). The results of the present study suggested that IL‑23 aggravated myocardial I/R injury by promoting inflammatory responses and myocardial apoptosis, which may be associated with high expression levels of IL‑17A and upregulation of the JAK2‑STAT3 signaling pathway.

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