The HMGB1‑IL‑17A axis contributes to hypoxia/reoxygenation injury via regulation of cardiomyocyte apoptosis and autophagy

Hu,Xiaorong; Zhang,Kai; Chen,Zhiqiang; Jiang,Hong; Xu,Weipan

doi:10.3892/mmr.2017.7839

The HMGB1‑IL‑17A axis contributes to hypoxia/reoxygenation injury via regulation of cardiomyocyte apoptosis and autophagy

Authors:
- Xiaorong Hu
- Kai Zhang
- Zhiqiang Chen
- Hong Jiang
- Weipan Xu
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Affiliations: 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 435000, P.R. China
Published online on: October 20, 2017 https://doi.org/10.3892/mmr.2017.7839
Pages: 336-341

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Abstract

Both the high‑mobility group box 1 protein (HMGB1) and interleukin (IL)‑17A serve important roles in myocardial ischemia and reperfusion injury. The purpose of the present study was to evaluate whether HMGB1 could induce IL‑17A secretion and lead to cardiomyocyte hypoxia/reoxygenation (H/R) injury. Neonatal rat cardiomyocytes were treated with HMGB1‑neutralizing antibody, IL‑17A‑neutralizing antibody, recombinant HMGB1 (rHMGB1) and recombinant IL‑17A (rIL‑17A), respectively. Cell viabilities, lactate dehydrogenase and creatine kinase levels were measured. Apoptotic cells were assessed by flow cytometry. The expression of HMGB1, IL‑17A, microtubule‑associated proteins 1A/1B light chain 3B (LC3), Beclin‑1, B‑cell lymphoma (Bcl)‑2 and Bcl‑2‑associated X protein were assessed by western blot analysis. The results demonstrated that HMGB1 significantly increased the expression of IL‑17A. HMGB1 or IL‑17A antibody significantly ameliorated H/R‑induced cell injury and improved the cell viability. In contrast, rHMGB1 or rIL‑17A aggravated cell injury and inhibited the cell viability. Furthermore, cardiomyocytes were treated with HMGB1 or IL‑17A antibody significantly increased Bcl‑2 protein expression and had fewer apoptotic cells, whereas rHMGB1 or rIL‑17A‑treated cardiomyocytes markedly decreased Bcl‑2 protein expression and had more apoptotic cells. Moreover, HMGB1 or IL‑17A antibodies significantly inhibited H/R induced autophagy dysfunction (as determined by the inhibition of Beclin‑1 expression, a lower ratio of LC3‑II to LC3‑I), whereas rHMGB1 or rIL‑17A may promote cardiomyocyte autophagy. Together, these results suggested that the HMGB1‑IL‑17A axis contributes to H/R injury via regulation of cardiomyocyte apoptosis and autophagy.

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