Effect of curcumin on lung epithelial injury and ferroptosis induced by cigarette smoke
Effect of curcumin on lung epithelial injury and ferroptosis induced by cigarette smoke
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DOI：
10.1177/09603271211059497
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发表时间：
2021-11-17
影响因子：
2.8
通讯作者：
Cao, Jie
中科院分区：
文献类型：
--
作者：
Tang, Xin;Li, Zhenyu;Cao, Jie
香烟烟雾(CS)引起的铁性下垂参与了COPD的发病机制，但其在肺上皮损伤和炎症中的作用尚不清楚。用CS或Cur处理BEAS-2B细胞，用CS提取液(CSE)、铁抑素-1(Fer-1)、去铁胺(DFO)或Cur处理BEAS-2B细胞，检测细胞内活性氧(ROS)积聚、脂质过氧化、铁超载和铁下垂相关蛋白的变化。与对照组相比，CSE处理的BEAS-2B细胞具有更多的细胞死亡、更高的细胞毒性和更低的细胞存活率。CS组大鼠支气管周围炎性细胞较正常组明显增多。同时，CSE/CS可提高BEAS-2B细胞和大鼠支气管肺泡灌洗液中IL-6和肿瘤坏死因子-α的水平。此外，在体外还观察到累积的ROS和耗尽的谷胱甘肽。在BEAS-2B细胞和大鼠肺组织中，CSE/CS增加丙二醛和铁，下调溶质载体家族7、谷胱甘肽过氧化物酶4和铁蛋白重链水平，上调转铁蛋白受体水平。这些变化在体外可被Fer-1或DFO所挽救，而在体内外可被Cur所缓解。综上所述，本研究表明铁下垂参与了CS诱导的肺上皮细胞损伤和炎症反应，而Cur可减轻CS诱导的肺上皮细胞损伤、炎症和铁下垂。
Cigarette smoke (CS)-caused ferroptosis was involved in the pathogenesis of COPD, but the role of ferroptosis in lung epithelial injury and inflammation is not clear. Rats were treated with CS or CUR and BEAS-2B cells were exposed to CS extract (CSE), ferrostatin-1 (Fer-1), deferoxamine (DFO), or CUR to detect reactive oxygen species (ROS) accumulation, lipid peroxidation, iron overload, and ferroptosis-related protein, which were the characteristic changes of ferroptosis. Compared with the control group, CSE-treated BEAS-2B cells had more cell death, higher cytotoxicity, and lower cell viability. The infiltration of inflammatory cell around the bronchi in the CS group of rats was more than that in the normal group. Meanwhile, CSE/CS elevated the levels of interleukin-6 and tumor necrosis factor-alpha in BEAS-2B cells and bronchoalveolar lavage fluid of rats. Besides, accumulative ROS and depleted glutathione was observed in vitro. In BEAS-2B cells and lung tissues of rats, CSE/CS increased malondialdehyde and iron; down-regulated solute carrier family 7, glutathione peroxidase 4, and ferritin heavy chain levels; and up-regulated transferrin receptor level. These changes were rescued by pretreatment of Fer-1 or DFO in vitro, and mitigated by CUR in vitro and in vivo. Collectively, this study reveals that ferroptosis was involved in lung epithelial cell injury and inflammation induced by CS, and CUR may alleviate CS-induced injury, inflammation, and ferroptosis of lung epithelial cell.