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-α 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.
Sphingolipid regulation of lung epithelial cell mitophagy and necroptosis during cigarette smoke exposure
