Jinshan Hospital Center for Tumor Diagnosis & Therapy, Fudan University, Shanghai, 201508, China.
Jinshan Hospital Center for Tumor Diagnosis & Therapy, Fudan University, Shanghai, 201508, China.
Biochem Biophys Res Commun. 2019 Nov 5;519(2):240-245. doi: 10.1016/j.bbrc.2019.08.165. Epub 2019 Sep 4.
Radiation-induced lung injury (RILI) is one of the most common and fatal complications of thoracic radiotherapy. Cell death is the critical point in RILI. Ferroptosis is discovered recently as a new type of cell death which is different from other forms. Our research investigated the role of ferroptosis in the process of acute RILI in mice. The levels of ROS in lungs and the inflammatory cytokine levels (TNF-α, IL-6, IL-10, and TGF-β1) in serum decreased significantly post ferroptosis inhibitor treatment in acute RILI. Ferroptotic characteristic changes of mitochondria in acute RILI was observed by transmission electron microscopy (TEM). Treatment with ferroptosis inhibitor significantly alleviated radiation-induced histopathological changes in mice lungs. Glutathione peroxidase 4 (GPX4), the key maker of the ferroptosis, was down-regulated in RILI. In summary, we observed that ferroptosis played a crucial role in acute RILI, and the ROS induced by irradaition might be the original trigger of ferroptosis in acute RILI. At the same time, ferroptosis may also affect the levels of inflammatory cytokines in acute RILI.
放射性肺损伤（RILI）是胸部放射治疗中最常见和最致命的并发症之一。细胞死亡是 RILI 的关键点。铁死亡是最近发现的一种不同于其他形式的新型细胞死亡。我们的研究调查了铁死亡在急性 RILI 小鼠模型中的作用。在急性 RILI 中，铁死亡抑制剂处理后，肺组织中 ROS 水平和血清中炎症细胞因子水平（TNF-α、IL-6、IL-10 和 TGF-β1）显著降低。透射电子显微镜（TEM）观察到急性 RILI 中线粒体的铁死亡特征性变化。铁死亡抑制剂处理可显著减轻辐射诱导的小鼠肺部组织学改变。谷胱甘肽过氧化物酶 4（GPX4）是铁死亡的关键调节因子，在 RILI 中下调。综上所述，我们观察到铁死亡在急性 RILI 中起关键作用，照射诱导的 ROS 可能是急性 RILI 中铁死亡的原始触发因素。同时，铁死亡也可能影响急性 RILI 中炎症细胞因子的水平。
