IL-27p28 敲除通过调节巨噬细胞极化加重阿霉素诱导的心脏毒性。
IL-27p28 knockout aggravates Doxorubicin-induced cardiotoxicity by regulating Macrophage polarization.
机构信息
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, The People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, China; Institute of Cardiovascular Diseases, Guangxi Academy of Medical Sciences, Nanning, China.
出版信息
Biochem Pharmacol. 2023 Apr;210:115469. doi: 10.1016/j.bcp.2023.115469. Epub 2023 Mar 1.
BACKGROUND
Several interleukins (ILs) have been demonstrated to participate in cardiac injury. This study aimed to investigate whether IL-27p28 plays a regulatory role in doxorubicin (DOX)-induced cardiac injury by regulating inflammation and oxidative stress.
METHODS
Dox was used to establish a mouse cardiac injury model, and IL-27p28 was knocked out to observe its role in cardiac injury. In addition, monocytes were adoptively transferred to clarify whether monocyte-macrophages mediate the regulatory role of IL-27p28 in DOX-induced cardiac injury.
RESULTS
IL-27p28 knockout significantly aggravated DOX-induced cardiac injury and cardiac dysfunction. IL-27p28 knockout also upregulated the phosphorylation levels of p65 and STAT1 and promoted M1 macrophage polarization in DOX-treated mice, which increased cardiac inflammation and oxidative stress. Moreover, IL-27p28-knockout mice that were adoptively transferred WT monocytes exhibited worse cardiac injury and cardiac dysfunction and higher cardiac inflammation and oxidative stress.
CONCLUSIONS
IL-27p28 knockdown aggravates DOX-induced cardiac injury by worsening the M1 macrophage/M2 macrophage imbalance and its associated inflammatory response and oxidative stress.
背景
已有研究表明，多种白细胞介素（ILs）参与心肌损伤。本研究旨在探讨白细胞介素 27p28（IL-27p28）是否通过调节炎症和氧化应激在阿霉素（DOX）诱导的心肌损伤中发挥调节作用。
方法
使用 DOX 建立小鼠心肌损伤模型，并敲除 IL-27p28 以观察其在心肌损伤中的作用。此外，通过过继转移单核细胞来阐明单核细胞-巨噬细胞是否介导 IL-27p28 在 DOX 诱导的心肌损伤中的调节作用。
结果
IL-27p28 敲除显著加重 DOX 诱导的心肌损伤和心功能障碍。IL-27p28 敲除还上调了 DOX 处理小鼠中 p65 和 STAT1 的磷酸化水平，并促进 M1 巨噬细胞极化，增加了心脏炎症和氧化应激。此外，过继转移 WT 单核细胞的 IL-27p28 敲除小鼠表现出更严重的心肌损伤和心功能障碍以及更高的心脏炎症和氧化应激。
结论
IL-27p28 敲低通过加重 M1 巨噬细胞/M2 巨噬细胞失衡及其相关炎症反应和氧化应激，加重 DOX 诱导的心肌损伤。
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