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SRC-mediated EGF Receptor Activation Regulates Ozone-induced Interleukin 8 Expression in Human Bronchial Epithelial Cells
Wu, W., P. Wages, R. Devlin, D. Diaz-Sanchez, D. Peden, AND J. Samet. SRC-mediated EGF Receptor Activation Regulates Ozone-induced Interleukin 8 Expression in Human Bronchial Epithelial Cells. ENVIRONMENTAL HEALTH PERSPECTIVES. National Institute of Environmental Health Sciences (NIEHS), Research Triangle Park, NC, 123(3):231-6, (2015).
Ozone exposure is a widespread public health concern, characterization of the mechanisms underlying ozone-induced airway inflammation will yield insights useful in the design of preventive and therapeutic interventions. The findings of this study show that exposure to O3 leads to Src-dependent EGFR activation leading to a pro-inflammatory response that includes IL-8 expression in human airway epithelial cells.
BACKGROUND: Human exposure to ozone (03) 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 03-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 03 (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 03 stimulation induced phosphorylation of Src at Y416, indicative of Src activation. Pharmacological inhibition of Src kinase activity abrogated 03-induced EGFR phosphorylation at tyrosines 1068 and 845. Moreover, pretreatment of BEAS-28 cells with inhibitor of either EGFR or Src kinase activities significantly blocked 03-induced IL-8 expression. CONCLUSION: 03 exposure increased IL-8 expression through Src-mediated EGFR transactivation in HBEC
Record Details:Record Type: DOCUMENT (JOURNAL/PEER REVIEWED JOURNAL)
Organization:U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF RESEARCH AND DEVELOPMENT
NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LABORATORY
ENVIRONMENTAL PUBLIC HEALTH DIVISION
CLINICAL RESEARCH BRANCH