气候变化领域集成服务门户

Human exposure to the highly reactive oxidant gas Ozone (O-3) 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-3-induced lung inflammation in mice. 40 BALB/c mice were exposed to filtered air (FA) or (0.25, 0.5, 1.00 ppm) O-3 for 3 h per day for 7 consecutive days. Levels of reactive oxygen species (ROS), EGF, and transforming growth factor alpha (TGF-alpha) 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-3 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-3 induced pronounced lung inflammation in a dose-dependent manner. Levels of ROS, TGF-alpha, and total proteins and cells in the BALF of mice exposed to 0.5 ppm or 1.0 ppm of O-3 were markedly elevated relative to those in the BALF of the mice exposed to FA. In addition, exposure to O-3 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-3 exposure. Inhalation of O-3 leads to inflammatory responses that are dependent on the activation the EGFR in the airway epithelium. (C) 2015 Wiley Periodicals, Inc.