Th17/IL-17 induces endothelial cell senescence via activation of NF-κB/p53/Rb signaling pathway
Th17/IL-17 induces endothelial cell senescence via activation of NF-κB/p53/Rb signaling pathway
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Th17/IL-17通过激活NF-κB/P53/Rb信号通路诱导内皮细胞衰老
DOI：
10.1038/s41374-021-00629-y
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发表时间：
2021-06
影响因子：
5
通讯作者：
Liang Zhang;Manli Liu;Wenhua Liu;Chaojie Hu;Hongqi Li;Jie Deng;Q. Cao;Yiping Wang;Wei Hu;Qing Li
中科院分区：
文献类型：
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作者：
Liang Zhang;Manli Liu;Wenhua Liu;Chaojie Hu;Hongqi Li;Jie Deng;Q. Cao;Yiping Wang;Wei Hu;Qing Li
细胞衰老是年龄相关性血管内皮功能障碍的关键机制。白细胞介素-17A（IL-17 A）是由Th 17细胞（辅助性T细胞的亚群）产生的炎性细胞因子，其是动脉粥样硬化发展的关键因素。然而，IL-17 A对血管内皮细胞衰老的影响仍不清楚。本研究旨在探讨IL-17 A在内皮细胞衰老中的作用及其相关信号通路。不同年龄小鼠脾脏Th 17细胞比例、IL-17 A、IL-6和血管细胞粘附分子-1（VCAM-1）表达水平均随增龄而升高。体外实验表明，IL-17 A可抑制小鼠主动脉内皮细胞（MAECs）增殖，增加衰老β-半乳糖苷酶和衰老相关蛋白（p16、p19、p21和p53）的表达。用吡咯烷二硫代氨基甲酸铵（PDTC）阻断NF-κB通路成功地抑制了IL-17 A诱导的衰老相关蛋白的表达。综上所述，我们的数据揭示了IL-17 A和内皮细胞衰老之间的一种先前未被怀疑的联系，这种联系是由NF-κB /p53/Rb通路介导的。
Cellular senescence is a key mechanism of age-related vascular endothelial dysfunction. Interleukin-17A (IL-17A) is an inflammatory cytokine produced by Th17 cells (a subgroup of helper T cells), which is a key factor in the development of atherosclerosis. However, the effect of IL-17A on the senescence of vascular endothelial cells is still unclear. In this study, we aimed to explore the role of IL-17A on endothelial cell senescence and its signaling pathways associated with senescence. The proportion of Th17 cells in the spleen and the expression levels of IL-17A, IL-6, and vascular cell adhesion molecule-1 (VCAM-1) in mice of different ages were increased with aging. In vitro experiments showed that proliferation was inhibited, senescent β-galactosidase and senescence-associated proteins (p16, p19, p21, and p53) of mouse aortic endothelial cells (MAECs) were increased with IL-17A treatment. Blocking the NF-κB pathway with ammonium pyrrolidinedithiocarbamate (PDTC) successfully inhibited IL-17A-induced expression of senescence-associated proteins. In conclusion, our data reveal a previously unsuspected link between IL-17A and endothelial cell senescence, which was mediated by the NF-κB /p53/Rb pathway.