Feng Feifei, Jin Yuefei, Duan Liju, Yan Zhen, Wang Shouying, Li Fangfang, Liu Yingying, Samet James M, Wu Weidong
College of Public Health, Zhengzhou University, Zhengzhou, China.
School of Public Health, Xinxiang Medical University, China.
Environ Toxicol. 2016 Dec;31(12):2016-2027. doi: 10.1002/tox.22202. Epub 2015 Oct 14.
Human exposure to the highly reactive oxidant gas Ozone (O ) is associated with inflammatory responses in the airway epithelium. The mechanisms responsible have not been fully elucidated. Epidermal growth factor receptor (EGFR) has previously been shown to play a critical role in the pathogenesis of lung inflammation. To define the role of EGFR in O -induced lung inflammation in mice. 40 BALB/c mice were exposed to filtered air (FA) or (0.25, 0.5, 1.00 ppm) O for 3 h per day for 7 consecutive days. Levels of reactive oxygen species (ROS), EGF, and transforming growth factor α (TGF-α) in the bronchoalveolar lavage fluid (BALF) of mice were measured using ELISA. BALB/c mice were intratracheally instilled with the EGFR kinase inhibitor PD153035 2 h prior to O exposure and every other day thereafter. Phosphorylation of EGFR (Y1068) in lung sections was determined using immunohistochemical staining and western blot 24 h after exposure. Inhalation of O induced pronounced lung inflammation in a dose-dependent manner. Levels of ROS, TGF-α, and total proteins and cells in the BALF of mice exposed to 0.5 ppm or 1.0 ppm of O were markedly elevated relative to those in the BALF of the mice exposed to FA. In addition, exposure to O induced EGFR(Y1068) phosphorylation in the airway epithelium. Administration of PD153035 resulted in a significantly reduced lung inflammation as well as EGFR phosphorylation induced by O exposure. Inhalation of O leads to inflammatory responses that are dependent on the activation the EGFR in the airway epithelium. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 2016-2027, 2016.
人类暴露于高活性氧化气体臭氧（O₃）会引发气道上皮的炎症反应。其背后的机制尚未完全阐明。此前已表明表皮生长因子受体（EGFR）在肺部炎症发病机制中起关键作用。为明确EGFR在臭氧诱导的小鼠肺部炎症中的作用，40只BALB/c小鼠连续7天每天暴露于过滤空气（FA）或0.25、0.5、1.00 ppm的臭氧中3小时。使用酶联免疫吸附测定法（ELISA）测量小鼠支气管肺泡灌洗液（BALF）中活性氧（ROS）、表皮生长因子（EGF）和转化生长因子α（TGF-α）的水平。在臭氧暴露前2小时及之后每隔一天，给BALB/c小鼠气管内注入EGFR激酶抑制剂PD153035。暴露24小时后，使用免疫组织化学染色和蛋白质印迹法测定肺组织切片中EGFR（Y1068）的磷酸化水平。吸入臭氧以剂量依赖方式引发明显的肺部炎症。相对于暴露于过滤空气的小鼠BALF中的水平，暴露于0.5 ppm或1.0 ppm臭氧的小鼠BALF中ROS、TGF-α以及总蛋白和细胞的水平显著升高。此外，暴露于臭氧会诱导气道上皮中EGFR（Y1068）磷酸化。给予PD153035可显著减轻臭氧暴露诱导的肺部炎症以及EGFR磷酸化。吸入臭氧会导致依赖于气道上皮中EGFR激活的炎症反应。© 2015威利期刊公司。《环境毒理学》31: 2016 - 2027, 2016年。
