基因剔除小鼠
氧化应激
p38丝裂原活化蛋白激酶
巨噬细胞
MAPK/ERK通路
M2巨噬细胞
细胞凋亡
过继性细胞移植
基因敲除
药理学
医学
免疫学
内分泌学
激酶
内科学
生物
细胞生物学
生物化学
免疫系统
受体
体外
T细胞
基因
作者
Jing Ye,Yuan Wang,Yao Xu,Zhen Wang,Ling Liu,Menglong Wang,Di Ye,Jishou Zhang,Zicong Yang,Yingzhong Lin,Qingwei Ji,Jun Wan
出处
期刊:Redox biology
[Elsevier BV]
日期:2020-07-08
卷期号:36: 101636-101636
被引量:32
标识
DOI:10.1016/j.redox.2020.101636
摘要
Several interleukin (IL) family members have been demonstrated to be involved in doxorubicin (DOX)-induced cardiac injury. This study aimed to investigate the role of IL-22 in DOX-induced cardiac injury and explore its possible mechanisms. In this study, mice were given DOX, and the cardiac expression and sources of IL-22 were determined. Then, IL-22 was knocked out to observe the effects on DOX-induced cardiac injury in mice. In addition, the p38 mitogen-activated protein kinase (MAPK) pathway was inhibited, macrophages were depleted and adoptively transferred, and Fizz3 was up-regulated in mice to explore the mechanisms. The results showed that cardiac IL-22 expression was significantly increased by DOX treatment and was mostly derived from cardiac macrophages. IL-22 knockout significantly reduced cardiac vacuolization and the expression of cardiomyocyte injury markers in both serum and left ventricular tissue and improved cardiac function in DOX-treated mice. In addition, IL-22 knockout reversed DOX-induced cardiac M1 macrophage/M2 macrophage imbalance, reduced oxidative stress and protected against cardiomyocyte apoptosis. p38 MAPK pathway inhibition with SB203580 and macrophage depletion further alleviated the above effects in DOX-treated IL-22-knockout mice. The effects were stronger IL-22-knockout mice with adoptive transfer of WT macrophages than in those with adoptive transfer of IL-22-knockout macrophages. Furthermore, increasing the expression of Fizz3 reduced cardiomyocyte apoptosis and alleviated cardiac dysfunction. Our results may suggest that IL-22 knockout alleviate DOX-induced oxidative stress and cardiac injury by inhibiting macrophage differentiation and thereby increasing the expression of Fizz3. Reductions in IL-22 expression may be beneficial for clinical chemotherapy in tumor patients.
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