Ferrostatin-1 alleviates lipopolysaccharide-induced acute lung injury via inhibiting ferroptosis
Ferrostatin-1 alleviates lipopolysaccharide-induced acute lung injury via inhibiting ferroptosis
复制标题
Ferrostatin-1 通过抑制铁死亡减轻脂多糖诱导的急性肺损伤
DOI：
10.1186/s11658-020-00205-0
复制
发表时间：
2020-02-27
影响因子：
8.3
通讯作者：
Zhao, Lei
中科院分区：
文献类型：
--
作者：
Liu, Pengfei;Feng, Yetong;Zhao, Lei
背景铁凋亡是一种新发现的细胞死亡类型，不同于传统的坏死、凋亡或自噬性细胞死亡。然而，铁凋亡在脂多糖（LPS）诱导的急性肺损伤（ALI）中的地位至今尚未得到深入研究。本研究主要分析铁凋亡与LPS诱导的ALI之间的关系。方法用脂多糖（LPS）和铁蛋白抑制剂ferrostatin-1（Fer-1，ferroptosis inhibitor）处理人支气管上皮细胞系BEAS-2B。使用CCK-8测量细胞活力。另外，在不同组中测量丙二醛（MDA）、4-羟基壬烯醛（4-HNE）和铁的水平，以及SLC 7A 11和GPX 4的蛋白水平。为了进一步证实体外结果，在小鼠中通过LPS诱导ALI模型，并评价Fer-1的治疗作用和肺组织中的铁凋亡水平。结果LPS处理后，BEAS-2B细胞存活率下降，铁凋亡标志物SLC 7A 11和GPX 4表达下降，MDA、4-HNE和总铁水平升高，且呈剂量依赖性，Fer-1可使细胞存活率下降。体内实验结果还表明，Fer-1对LPS诱导的ALI具有治疗作用，并下调肺组织中的铁凋亡水平。结论铁凋亡在LPS诱导的ALI的发生发展中起重要作用，可能成为治疗ALI的新靶点。
Background Ferroptosis is a newly recognized type of cell death, which is different from traditional necrosis, apoptosis or autophagic cell death. However, the position of ferroptosis in lipopolysaccharide (LPS)-induced acute lung injury (ALI) has not been explored intensively so far. In this study, we mainly analyzed the relationship between ferroptosis and LPS-induced ALI. Methods In this study, a human bronchial epithelial cell line, BEAS-2B, was treated with LPS and ferrostatin-1 (Fer-1, ferroptosis inhibitor). The cell viability was measured using CCK-8. Additionally, the levels of malondialdehyde (MDA), 4-hydroxynonenal (4-HNE), and iron, as well as the protein level of SLC7A11 and GPX4, were measured in different groups. To further confirm the in vitro results, an ALI model was induced by LPS in mice, and the therapeutic action of Fer-1 and ferroptosis level in lung tissues were evaluated. Results The cell viability of BEAS-2B was down-regulated by LPS treatment, together with the ferroptosis markers SLC7A11 and GPX4, while the levels of MDA, 4-HNE and total iron were increased by LPS treatment in a dose-dependent manner, which could be rescued by Fer-1. The results of the in vivo experiment also indicated that Fer-1 exerted therapeutic action against LPS-induced ALI, and down-regulated the ferroptosis level in lung tissues. Conclusions Our study indicated that ferroptosis has an important role in the progression of LPS-induced ALI, and ferroptosis may become a novel target in the treatment of ALI patients.