Liproxstatin-1通过抑制铁死亡减轻LPS/IL-13诱导的小鼠支气管上皮细胞损伤和中性粒细胞性哮喘
2022/07/19
摘要
背景：铁死亡与呼吸道疾病密切相关；然而，铁死亡与中性粒细胞性哮喘之间的关系尚不清楚。
目的：本研究探讨了Liproxstatin-1(Lip-1)是否通过抑制铁死亡和炎症反应来影响中性粒细胞性哮喘的进展，同时分析了潜在的分子机制。
方法：用脂多糖(LPS)和白细胞介素-13 (IL-13)分别给药支气管上皮细胞16HBE和BEAS-2B，建立细胞损伤模型。我们利用这个细胞模型来研究Lip-1对气道上皮相关炎症和铁死亡的影响以及潜在的分子机制。同时，我们利用卵白蛋白(OVA)/LPS诱导的小鼠模型评估了Lip-1对中性粒细胞性哮喘和铁死亡的影响。
结果：Lip-1可以逆转LPS和IL-13作用下HBE和BEAS-2B细胞中铁死亡调节剂(谷胱甘肽过氧化物酶4 (GPX4)、可溶性载体家族7成员11 (SLC7A11)和前列腺素-内过氧化物合酶2 (PTGS2))的表达变化，降低脂质活性氧(脂质ROS)，改善细胞活力。此外，Lip-1处理可显著降低HBE和BEAS-2B细胞中IL-33、TSLP、IL-8、IL-6和HMGB1的表达。同时，Lip-1可明显缓解OVA/LPS诱导的中性粒细胞性哮喘，表现为肺病理改变、气道粘液分泌、炎症和铁死亡明显改善。
结论：本研究提供的数据表明，Lip-1可以通过抑制铁死亡，在体内和体外减轻中性粒细胞性哮喘，可能为中性粒细胞性哮喘的治疗提供一种新的策略。
Liproxstatin-1 alleviates LPS/IL-13-induced bronchial epithelial cell injury and neutrophilic asthma in mice by inhibiting ferroptosis
Bao C, Liu C, Liu Q, et al.
Abstract
BACKGROUND：Ferroptosis is closely associated with respiratory diseases; however, the relationship between ferroptosis and neutrophilic asthma remains unknown.
OBJECTIVE: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.
CONCLUSIONS: 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.
背景：铁死亡与呼吸道疾病密切相关；然而，铁死亡与中性粒细胞性哮喘之间的关系尚不清楚。
目的：本研究探讨了Liproxstatin-1(Lip-1)是否通过抑制铁死亡和炎症反应来影响中性粒细胞性哮喘的进展，同时分析了潜在的分子机制。
方法：用脂多糖(LPS)和白细胞介素-13 (IL-13)分别给药支气管上皮细胞16HBE和BEAS-2B，建立细胞损伤模型。我们利用这个细胞模型来研究Lip-1对气道上皮相关炎症和铁死亡的影响以及潜在的分子机制。同时，我们利用卵白蛋白(OVA)/LPS诱导的小鼠模型评估了Lip-1对中性粒细胞性哮喘和铁死亡的影响。
结果：Lip-1可以逆转LPS和IL-13作用下HBE和BEAS-2B细胞中铁死亡调节剂(谷胱甘肽过氧化物酶4 (GPX4)、可溶性载体家族7成员11 (SLC7A11)和前列腺素-内过氧化物合酶2 (PTGS2))的表达变化，降低脂质活性氧(脂质ROS)，改善细胞活力。此外，Lip-1处理可显著降低HBE和BEAS-2B细胞中IL-33、TSLP、IL-8、IL-6和HMGB1的表达。同时，Lip-1可明显缓解OVA/LPS诱导的中性粒细胞性哮喘，表现为肺病理改变、气道粘液分泌、炎症和铁死亡明显改善。
结论：本研究提供的数据表明，Lip-1可以通过抑制铁死亡，在体内和体外减轻中性粒细胞性哮喘，可能为中性粒细胞性哮喘的治疗提供一种新的策略。
（中日友好医院呼吸与危重症医学科 李春晓 摘译 林江涛 审校）
（International Immunopharmacology, 2022, 109 doi: ARTN 10877010.1016/j.intimp.2022.108770）
（International Immunopharmacology, 2022, 109 doi: ARTN 10877010.1016/j.intimp.2022.108770）
Liproxstatin-1 alleviates LPS/IL-13-induced bronchial epithelial cell injury and neutrophilic asthma in mice by inhibiting ferroptosis
Bao C, Liu C, Liu Q, et al.
Abstract
BACKGROUND：Ferroptosis is closely associated with respiratory diseases; however, the relationship between ferroptosis and neutrophilic asthma remains unknown.
OBJECTIVE: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.
CONCLUSIONS: 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.
上一篇：
烟草烟雾可通过诱导记忆样3型先天淋巴细胞加重哮喘
下一篇：
重度哮喘患者气道上皮细胞Axl表达降低与嗜酸性炎症相关
