山西医科大学学报2025，Vol.56Issue(4)：390-397,8.DOI:10.13753/j.issn.1007-6611.2025.04.007
CISD2抑制铁死亡减轻气道上皮细胞炎症损伤
CISD2 mitigates inflammatory damage of airway epithelial cells by suppressing ferroptosis
摘要
Abstract
Objective To investigate the role of cysteine-aspartic acid-glycine-serine-histidine(CDGSH)iron-sulfur domain 2(CISD2)in modulating inflammatory damage and ferroptosis in airway epithelial cells,and explore its possible molecular mechanism.Methods A recombinant lentivirus(LV)expressing CISD2 was constructed and introduced into the human bronchial epithelial cells BEAS-2B to achieve CISD2 overexpression.The airway epithelial cell injury model was established by stimulating BEAS-2B cells with lipopolysaccharide(LPS)and interleukin-13(IL-13).BEAS-2B cells were divided into control group,model group,model+LV-Ctrl group,model+LV-CISD2 group,and model+LV-CISD2 group+ML385(Nrf2 inhibitor)group.Western blot was performed to detect the protein expressions of CISD2,nuclear factor erythroid 2-related factor 2(Nrf2),solute carrier family 7 member 11(SLC7A11),and glutathione peroxidase 4(GPX4).Cell counting kit-8(CCK-8)assay was employed to assess the cell viability.Enzyme-linked im-munosorbent assay(ELISA)was utilized to detect the expression levels of IL-6 and IL-8.Lipid peroxidation was determined using the C11-BODIPY fluorescent probe.The levels of malondialdehyde(MDA),glutathione(GSH),and iron were measured using relevant kits.Results Compared with control group,the expression of CISD2 was decreased in model group and model+LV-Ctrl group(P<0.01).Compared with model group and model+LV-Ctrl group,the expression of CISD2 was increased in model+LV-CISD2 group(P<0.01).Compared with control group,the cell viability was reduced(P<0.01),the expressions of IL-6 and IL-8 were increased(P<0.05),the levels of lipid peroxidation and iron were upregulated(P<0.01),the expression of Nrf2 was increased(P<0.05),and the ex-pressions of SLC7A11 and GPX4 were decreased in model group and model+LV-Ctrl group(P<0.01).Compared with model group and model+LV-Ctrl group,the cell viability was increased(P<0.01),the expressions of IL-6 and IL-8 were reduced(P<0.05),the levels of lipid peroxidation and iron were downregulated(P<0.01),the expressions of Nrf2,SLC7A11 and GPX4 were increased in model+LV-CISD2 group(P<0.01).Compared with model+LV-CISD2 group,the expressions of Nrf2,SLC7A11 and GPX4 were reduced(P<0.01),the cell viability was decreased(P<0.01),and the levels of lipid peroxidation and iron were upregulated in model+LV-CISD2+ML385 group(P<0.01).Conclusion Overexpression of CISD2 can alleviate the inflammatory damage in airway epithelial cells,which may be related to the inhibition of ferroptosis by regulating the Nrf2-SLC7A11/GPX4 signaling pathway.关键词
哮喘/气道上皮细胞/炎症损伤/铁死亡/CISD2/脂质过氧化/Nrf2Key words
asthma/airway epithelial cells/inflammatory injury/ferroptosis/CISD2/lipid peroxidation/Nrf2分类
临床医学引用本文复制引用
陈雪,宁谦..CISD2抑制铁死亡减轻气道上皮细胞炎症损伤[J].山西医科大学学报,2025,56(4):390-397,8.基金项目
陕西省重点研发计划项目(2022SF-141) （2022SF-141）
