RT Journal Article
SR Electronic
T1 Induction of ferroptosis-like cell death of eosinophils exerts synergistic effects with glucocorticoids in allergic airway inflammation
JF Thorax
JO Thorax
FD BMJ Publishing Group Ltd and British Thoracic Society
SP 918
OP 927
DO 10.1136/thoraxjnl-2020-214764
VO 75
IS 11
A1 Yanping Wu
A1 Haixia Chen
A1 Nanxia Xuan
A1 Lingren Zhou
A1 Yinfang Wu
A1 Chen Zhu
A1 Miao Li
A1 Qingyu Weng
A1 Jiaxin Shen
A1 Hao Zhang
A1 Bin Zhang
A1 Fen Lan
A1 Lixia Xia
A1 Xuefang Xiong
A1 Zhouyang Li
A1 Yun Zhao
A1 Mindan Wu
A1 Songmin Ying
A1 Wen Li
A1 Huahao Shen
A1 Zhihua Chen
YR 2020
UL http://thorax.bmj.com/content/75/11/918.abstract
AB Introduction Eosinophils are critical in allergic disorders, and promoting eosinophil death effectively attenuates allergic airway inflammation. Ferroptosis is a recently described novel form of cell death; however, little is known about ferroptosis in eosinophils and related diseases. This study aimed to investigate the effects of ferroptosis-inducing agents (FINs) on eosinophil death and allergic airway inflammation, and to explore their potential synergistic effect with glucocorticoids (GCs).Methods Eosinophils isolated from the peripheral blood of humans or mice were incubated with FINs, and eosinophil ferroptosis was assessed. The in vivo effects of FINs alone or in combination with dexamethasone (DXMS) were examined in a mouse model of allergic airway inflammation. Bronchoalveolar lavage fluid and lung tissue were collected to examine airway inflammation.Results Treatment with FINs time and dose dependency induced cell death in human and mouse eosinophils. Interestingly, FINs induced non-canonical ferroptosis in eosinophils, which generated morphological characteristics unique to ferroptosis and was iron dependent but was independent of lipid peroxidation. The antioxidants glutathione and N-acetylcysteine significantly attenuated FIN-induced cell death. Treatment with FINs triggered eosinophil death in vivo and eventually relieved eosinophilic airway inflammation in mice. Furthermore, FINs exerted a synergistic effect with DXMS to induce eosinophil death in vitro and to alleviate allergic airway inflammation in vivo.Conclusions FINs induced ferroptosis-like cell death of eosinophils, suggesting their use as a promising therapeutic strategy for eosinophilic airway inflammation, especially due to the advantage of their synergy with GCs in the treatment of allergic disorders.