title: SRC-mediated EGF receptor activation regulates ozone-induced interleukin 8 expression in human bronchial epithelial cells.
abstract: BACKGROUND
  Human exposure to ozone (O3) results in pulmonary function decrements and airway inflammation. The mechanisms underlying these adverse effects remain unclear. Epidermal growth factor receptor (EGFR) plays an important role in the pathogenesis of lung inflammation.
  
  
  OBJECTIVE
  We examined the role of EGFR activation in O3-induced expression of the chemokine interleukin 8 (IL-8) in human bronchial epithelial cells (HBEC).
  
  
  METHODS
  We detected phosphorylated EGFR using immunoblotting. EGFR dimerization was examined through cross-linking reaction and immunoblotting, and levels of IL-8 protein were measured using ELISA.
  
  
  RESULTS
  Exposure to O3 (0.25-1.0 ppm) induced rapid and marked increase in EGFR phosphorylation at the autophosphorylation site Y1068 and the transphosphorylation site Y845, implicating the involvement of Src kinase. Further investigation showed that O3 stimulation induced phosphorylation of Src at Y416, indicative of Src activation. Pharmacological inhibition of Src kinase activity abrogated O3-induced EGFR phosphorylation at tyrosines 1068 and 845. Moreover, pretreatment of BEAS-2B cells with inhibitor of either EGFR or Src kinase activities significantly blocked O3-induced IL-8 expression.
  
  
  CONCLUSIONS
  O3 exposure increased IL-8 expression through Src-mediated EGFR transactivation in HBEC.
authors.affiliation: School of Public Health, Xinxiang Medical University, Xinxiang, Henan Province, China.
authors.forename: Weidong
authors.initials: W
authors.lastname: Wu
authors.forename: Phillip A
authors.initials: PA
authors.lastname: Wages
authors.forename: Robert B
authors.initials: RB
authors.lastname: Devlin
authors.forename: David
authors.initials: D
authors.lastname: Diaz-Sanchez
authors.forename: David B
authors.initials: DB
authors.lastname: Peden
authors.forename: James M
authors.initials: JM
authors.lastname: Samet
mesh_terms: D000393:Air Pollutants / Q000633:toxicity*; D001980:Bronchi / Q000166:cytology; D002460:Cell Line; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000187:drug effects; D066246:ErbB Receptors / Q000378:metabolism*; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism*; D010126:Ozone / Q000633:toxicity*; D010766:Phosphorylation / Q000187:drug effects; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: D000393:Air Pollutants; D016209:Interleukin-8; D010126:Ozone; D066246:ErbB Receptors; D019061:src-Family Kinases