Ozone is one of the criteria air pollutants.Controlled human inhalation and experimental animal studies have demonstrated that ozone exposure could induce neutrophilic airway inflammation.The mechanisms underlying this event remain unclear.It has been shown that ozone exposure increased expression of EGF receptor(EGFR)and its ligands in human nasal epithelium.This study aimed to examine the role of EGFR in ozone-induced inflammatory response in human bronchial epithelial cell line,BEAS-2B.Exposure to ozone(0.25-1ppm)induced rapid and marked increase in EGFR phosphorylation at tyrosines 1068 and 845,implying the involvement of Src kinase.Indeed,further studies showed that ozone stimulation induced phosphorylation of Src at tyrosine 416,indicative of Src activation.Pharmacological inhibition of Src kinase abrogated ozone-induced EGFR phosprylation at tyrosines 1068 and 845.Moreover,pretreatment of BEAS-2B cells with either EGFR or Src kinase inhibitor significantly blocked ozone-induced interleukin 8(IL-8)over-expressions.Ozone exposure induced reactive oxygen species(ROS)production and NF-κB activation.Pharmacological inhibition of NF-κB activation or mutation of the IL-8 promoter at the κB-binding site significantly blocked ozone-induced IL-8 production or IL-8 transcriptional activity,respectively.Knockdown of GSTM1 in BEAS-2B cells enhanced ozone-induced NF-κB activation and IL-8 production.Consistently,an ozone-induced overt increase in IL-8 production was detected in GSTM1-null primary human bronchial epithelial cells.In addition,supplementation with reduced GSH inhibited ozone-induced ROS production,NF-κB activation,and IL-8 production.Taken together,these results indicated that ozone exposure increased IL-8 expression through Src-mediated EGFR activation in human bronchial epithelial cells.GSTM1 deficiency enhances ozone-induced IL-8 production,which is mediated by generated ROS and subsequent NF-κB activation in human bronchial epithelial cells.