Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China; Cardiovascular Research Institute, Wuhan University, Wuhan 430060, China; Hubei Key Laboratory of Cardiology, Wuhan, China.
Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China; Cardiovascular Research Institute, Wuhan University, Wuhan 430060, China; Hubei Key Laboratory of Cardiology, Wuhan, China.
Life Sci. 2020 Aug 15;255:117844. doi: 10.1016/j.lfs.2020.117844. Epub 2020 May 25.
Interleukin (IL) 9 is a pleiotropic cytokine, and recent studies have demonstrated that IL-9 is associated with several cardiovascular diseases, via regulation of the inflammatory response. Doxorubicin (DOX) is known to induce severe cardiac injury and dysfunction by enhancing inflammation. This study aimed to investigate the role of IL-9 in DOX-induced cardiotoxicity.
DOX was used to induce cardiac dysfunction and the expression of IL-9 in the murine cardiac tissues was measured. The mice were intraperitoneally injected with recombinant mouse IL-9 (rmIL-9) or anti-IL-9 neutralizing antibody (IL-9nAb) for investigating the effect of IL-9 on DOX-induced cardiac injury and dysfunction. The messenger ribonucleic acid (mRNA) expression levels of the pro-inflammatory cytokines were determined in each group by quantitative real-time polymerase chain reaction (RT-qPCR). The effect of rmIL-9 or IL-9nAb on DOX-induced apoptosis was determined both in vivo and vitro.
IL-9 levels significantly increased in the heart following DOX injection. Cardiac injury and dysfunction were induced by DOX, and treatment with IL-9nAb significantly alleviated DOX-induced injury, whereas rmIL-9 administration aggravated the cardiac damage. IL-9nAb decreased the expression of pro-inflammatory cytokines in the DOX-treated mice, while rmIL-9 administration increased the levels of pro-inflammatory cytokines. IL-9nAb reduced DOX-induced myocardial apoptosis, whereas rmIL-9 administration produced the opposite results. Additionally, IL-9nAb mitigated the DOX-induced apoptosis in H9C2 cells, while administration of rmIL-9 produced the opposite effect.
Our results demonstrated that IL-9 aggravated DOX-induced cardiac injury and dysfunction by promoting the inflammatory response and cardiomyocyte apoptosis.
白细胞介素（IL）9 是一种多效细胞因子，最近的研究表明，IL-9 通过调节炎症反应与几种心血管疾病有关。多柔比星（DOX）已知通过增强炎症而导致严重的心脏损伤和功能障碍。本研究旨在探讨 IL-9 在 DOX 诱导的心脏毒性中的作用。
使用 DOX 诱导心脏功能障碍，并测量小鼠心脏组织中 IL-9 的表达。通过腹腔内注射重组小鼠 IL-9（rmIL-9）或抗 IL-9 中和抗体（IL-9nAb）来研究 IL-9 对 DOX 诱导的心脏损伤和功能障碍的影响。通过定量实时聚合酶链反应（RT-qPCR）确定每组中促炎细胞因子的信使核糖核酸（mRNA）表达水平。体内和体外测定 rmIL-9 或 IL-9nAb 对 DOX 诱导的细胞凋亡的影响。
DOX 注射后心脏中 IL-9 水平显著增加。DOX 诱导心脏损伤和功能障碍，而 IL-9nAb 治疗可显著减轻 DOX 诱导的损伤，而 rmIL-9 给药则加重心脏损伤。IL-9nAb 降低 DOX 处理小鼠中促炎细胞因子的表达，而 rmIL-9 给药则增加促炎细胞因子的水平。IL-9nAb 减少 DOX 诱导的心肌细胞凋亡，而 rmIL-9 给药则产生相反的结果。此外，IL-9nAb 减轻了 DOX 在 H9C2 细胞中诱导的凋亡，而 rmIL-9 给药则产生相反的效果。
我们的结果表明，IL-9 通过促进炎症反应和心肌细胞凋亡加重 DOX 诱导的心脏损伤和功能障碍。
