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. 2022 Aug:109:108770.
doi: 10.1016/j.intimp.2022.108770. Epub 2022 Apr 25.

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

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

Chen Bao et al. Int Immunopharmacol. 2022 Aug.
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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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