title: 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) O3for 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 O3exposure 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 O3induced 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 O3were markedly elevated relative to those in the BALF of the mice exposed to FA. In addition, exposure to O3induced EGFR(Y1068) phosphorylation in the airway epithelium. Administration of PD153035 resulted in a significantly reduced lung inflammation as well as EGFR phosphorylation induced by O3exposure. Inhalation of O3leads 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.
authors.affiliation: College of Public Health, Zhengzhou University, Zhengzhou, China.
authors.forename: Feifei
authors.initials: F
authors.lastname: Feng
authors.affiliation: College of Public Health, Zhengzhou University, Zhengzhou, China.
authors.forename: Yuefei
authors.initials: Y
authors.lastname: Jin
authors.affiliation: College of Public Health, Zhengzhou University, Zhengzhou, China.
authors.forename: Liju
authors.initials: L
authors.lastname: Duan
authors.affiliation: College of Public Health, Zhengzhou University, Zhengzhou, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Yan
authors.affiliation: School of Public Health, Xinxiang Medical University, China.
authors.forename: Shouying
authors.initials: S
authors.lastname: Wang
authors.affiliation: School of Public Health, Xinxiang Medical University, China.
authors.forename: Fangfang
authors.initials: F
authors.lastname: Li
authors.affiliation: School of Public Health, Xinxiang Medical University, China.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, United States Environmental Protection Agency, Chapel Hill, North Carolina.
authors.forename: James M
authors.initials: JM
authors.lastname: Samet
authors.affiliation: School of Public Health, Xinxiang Medical University, China.
authors.forename: Weidong
authors.initials: W
authors.lastname: Wu
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005260:Female; D008168:Lung / Q000378:metabolism; D008297:Male; D008807:Mice, Inbred BALB C; D010126:Ozone / Q000633:toxicity*; D010766:Phosphorylation; D011014:Pneumonia / Q000139:chemically induced / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D016211:Transforming Growth Factor alpha / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D016211:Transforming Growth Factor alpha; D010126:Ozone; C541485:EGFR protein, mouse; D066246:ErbB Receptors
keywords: TGF-α; epidermal growth factor receptor; lung inflammation; ozone