1. Academic Validation
  2. Liproxstatin-1 alleviates LPS/IL-13-induced bronchial epithelial cell injury and neutrophilic asthma in mice by inhibiting ferroptosis

Liproxstatin-1 alleviates LPS/IL-13-induced bronchial epithelial cell injury and neutrophilic asthma in mice by inhibiting ferroptosis

  • Int Immunopharmacol. 2022 Aug;109:108770. doi: 10.1016/j.intimp.2022.108770.
Chen Bao 1 Chao Liu 1 Qian Liu 1 Lijuan Hua 1 Jiannan Hu 1 Ziling Li 1 Shuyun Xu 2
Affiliations

Affiliations

  • 1 Department of Respiratory and Critical Care Medicine, Key Laboratory of Pulmonary Diseases of Health Ministry, Key Site of National Clinical Research Center for Respiratory Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China.
  • 2 Department of Respiratory and Critical Care Medicine, Key Laboratory of Pulmonary Diseases of Health Ministry, Key Site of National Clinical Research Center for Respiratory Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China.. Electronic address: sxu@hust.edu.cn.
Abstract

Background and purpose: Ferroptosis is closely associated with respiratory diseases; however, the relationship between Ferroptosis and neutrophilic asthma remains unknown. This study investigated whether Liproxstatin-1 (Lip-1) affects the progression of neutrophilic asthma by inhibiting Ferroptosis and inflammatory response, while dissecting the underlying molecular mechanisms.

Methods: The bronchial epithelial cells (16HBE and BEAS-2B) were administered with lipopolysaccharide (LPS) and interleukin-13 (IL-13) to generate a cell injury model. This cell model was employed to examine the effect of Lip-1 on airway epithelial-associated inflammation and Ferroptosis as well as the underlying molecular mechanism. Meanwhile, we evaluated the effects of Lip-1 on neutrophilic asthma and Ferroptosis by using the ovalbumin (OVA)/LPS-induced mouse model.

Results: Lip-1 reversed the altered expression of ferroptotic regulators (Glutathione Peroxidase 4 (GPX4), solute carrier family 7 member 11 (SLC7A11) and prostaglandin-endoperoxide synthase 2 (PTGS2)), attenuated lipid Reactive Oxygen Species (lipid ROS) and ameliorated cell viability in HBE and BEAS-2B cells administered with LPS and IL-13. Moreover, Lip-1 treatment led to a marked reduction in the expression of IL-33, TSLP, IL-8, IL-6, and HMGB1 in the HBE and BEAS-2B cells. In the meantime, administration with Lip-1 markedly relieved OVA/LPS-induced neutrophilic asthma, as indicated by significant improvement in lung pathological changes, airway mucus secretion, inflammation, and Ferroptosis.

Conclusion: This study provides data suggesting that Lip-1 alleviates neutrophilic asthma in vivo and in vitro through inhibiting Ferroptosis, perhaps providing a new strategy for neutrophilic asthma treatment.

Keywords

Bronchial epithelial cell; Ferroptosis; Glutathione peroxidase 4; Liproxstatin-1; Neutrophilic asthma; Solute carrier family 7 member 11.

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