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

Abstract

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.