CC16通过抑制铁突变减轻PM2.5诱导的哮喘小鼠肺上皮细胞损伤和气道炎症
2025/01/26
摘要
背景：暴露于 PM2.5 是一项重大的公共卫生挑战，与哮喘的恶化密切相关，而哮喘仍然缺乏有效的预防措施。Club细胞 16 kDa 蛋白（CC16）具有抗炎和抗氧化特性，可能对 PM2.5 导致的哮喘恶化具有保护作用；然而，人们对其潜在机制，尤其是与铁氧化相关的机制仍知之甚少。
方法：使用暴露于PM2.5的TC-1肺上皮细胞模型以及同样暴露于PM2.5的卵清蛋白（OVA）诱导的哮喘小鼠模型，评估CC16对炎症和铁蛋白沉积的影响。
结果：CC16能明显调节PM2.5暴露的肺上皮细胞中的铁氧化关键调节因子（NRF2、GPX4、SLC7A11、HO-1），并减少促炎细胞因子（IL-13、IL-5、IL-6、IL-1β、IL-17A）。此外，它还增强了肺功能，同时减少了气道炎症和粘液分泌，并抑制了 PM2.5 诱导的哮喘小鼠的铁变态反应。
结论：CC16通过调节铁蛋白沉积和减轻气道炎症，有望成为治疗PM2.5诱导的哮喘的药物，从而为哮喘治疗提供一种新策略。
CC16 alleviates PM2.5-induced lung epithelial cell injury and airway inflammation in asthmatic mice by inhibiting ferroptosis
Wang, A., Liu, J., Li, Z., Qian, Z., Yang, S., Luo, S., Lin, J., & Wu, J.
Abstract
Background:Exposure to PM2.5 represents a significant public health challenge, closely associated with the worsening of asthma, a condition that still lacks effective preventive measures. Club Cell 16 kDa protein (CC16), recognized for its anti-inflammatory and antioxidant properties, may serve a protective function in asthma exacerbated by PM2.5; however, the underlying mechanisms, particularly those related to ferroptosis, remain poorly understood.
Methods:The impact of CC16 on inflammation and ferroptosis was assessed using a TC-1 lung epithelial cell model exposed to PM2.5, as well as an ovalbumin (OVA)-induced asthmatic mouse model also subjected to PM2.5 exposure.
Results:CC16 significantly modulated key regulators of ferroptosis (NRF2, GPX4, SLC7A11, HO-1) and attenuated pro-inflammatory cytokines (IL-13, IL-5, IL-6, IL-1β, IL-17A) in PM2.5-exposed lung epithelial cells. Furthermore, it enhanced pulmonary function while reducing airway inflammation and mucus secretion and inhibited ferroptosis in PM2.5-induced asthmatic mice.
Conclusion:CC16 demonstrates promise as a therapeutic agent for PM2.5-induced asthma by modulating ferroptosis and alleviating airway inflammation, thereby providing a novel strategy for asthma management.
背景：暴露于 PM2.5 是一项重大的公共卫生挑战，与哮喘的恶化密切相关，而哮喘仍然缺乏有效的预防措施。Club细胞 16 kDa 蛋白（CC16）具有抗炎和抗氧化特性，可能对 PM2.5 导致的哮喘恶化具有保护作用；然而，人们对其潜在机制，尤其是与铁氧化相关的机制仍知之甚少。
方法：使用暴露于PM2.5的TC-1肺上皮细胞模型以及同样暴露于PM2.5的卵清蛋白（OVA）诱导的哮喘小鼠模型，评估CC16对炎症和铁蛋白沉积的影响。
结果：CC16能明显调节PM2.5暴露的肺上皮细胞中的铁氧化关键调节因子（NRF2、GPX4、SLC7A11、HO-1），并减少促炎细胞因子（IL-13、IL-5、IL-6、IL-1β、IL-17A）。此外，它还增强了肺功能，同时减少了气道炎症和粘液分泌，并抑制了 PM2.5 诱导的哮喘小鼠的铁变态反应。
结论：CC16通过调节铁蛋白沉积和减轻气道炎症，有望成为治疗PM2.5诱导的哮喘的药物，从而为哮喘治疗提供一种新策略。
(中日友好医院呼吸与危重症医学科 沈焜路 摘译 林江涛 审校)
(Ecotoxicol Environ Saf. 2024 Dec 6; DOI: 10.1016/j.ecoenv.2024.117417)
(Ecotoxicol Environ Saf. 2024 Dec 6; DOI: 10.1016/j.ecoenv.2024.117417)
CC16 alleviates PM2.5-induced lung epithelial cell injury and airway inflammation in asthmatic mice by inhibiting ferroptosis
Wang, A., Liu, J., Li, Z., Qian, Z., Yang, S., Luo, S., Lin, J., & Wu, J.
Abstract
Background:Exposure to PM2.5 represents a significant public health challenge, closely associated with the worsening of asthma, a condition that still lacks effective preventive measures. Club Cell 16 kDa protein (CC16), recognized for its anti-inflammatory and antioxidant properties, may serve a protective function in asthma exacerbated by PM2.5; however, the underlying mechanisms, particularly those related to ferroptosis, remain poorly understood.
Methods:The impact of CC16 on inflammation and ferroptosis was assessed using a TC-1 lung epithelial cell model exposed to PM2.5, as well as an ovalbumin (OVA)-induced asthmatic mouse model also subjected to PM2.5 exposure.
Results:CC16 significantly modulated key regulators of ferroptosis (NRF2, GPX4, SLC7A11, HO-1) and attenuated pro-inflammatory cytokines (IL-13, IL-5, IL-6, IL-1β, IL-17A) in PM2.5-exposed lung epithelial cells. Furthermore, it enhanced pulmonary function while reducing airway inflammation and mucus secretion and inhibited ferroptosis in PM2.5-induced asthmatic mice.
Conclusion:CC16 demonstrates promise as a therapeutic agent for PM2.5-induced asthma by modulating ferroptosis and alleviating airway inflammation, thereby providing a novel strategy for asthma management.
上一篇：
没有了
下一篇：
缺氧诱导因子2α通过调节磷脂代谢促进干细胞样Th2细胞的致病极化
