Regulation of ozone‐induced lung inflammation by the epidermal growth factor receptor in mice

Human exposure to the highly reactive oxidant gas Ozone (O₃) 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 O₃‐induced lung inflammation in mice. 40 BALB/c mice were exposed to filtered air (FA) or (0.25, 0.5, 1.00 ppm) O₃ 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 O₃ 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 O₃ 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 O₃ were markedly elevated relative to those in the BALF of the mice exposed to FA. In addition, exposure to O₃ 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 O₃ exposure. Inhalation of O₃ 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.