Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10738085 | Free Radical Biology and Medicine | 2011 | 8 Pages |
Abstract
Exposure to the major air pollutant ozone can aggravate asthma and other lung diseases. Our recent study in human volunteers has shown that the glutathione S-transferase Mu 1 (GSTM1)-null genotype is associated with increased airway neutrophilic inflammation induced by inhaled ozone. The aim of this study was to examine the effect of GSTM1 modulation on interleukin 8 (IL-8) production in ozone-exposed human bronchial epithelial cells (BEAS-2B) and the underlying mechanisms. Exposure of BEAS-2B cells to 0.4 ppm ozone for 4 h significantly increased IL-8 release, with a modest reduction in intracellular reduced glutathione (GSH). 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, GSTM1 deficiency enhances ozone-induced IL-8 production, which is mediated by generated ROS and subsequent NF-κB activation in human bronchial epithelial cells.
Keywords
EGFKBMm.o.i.PBSglutathione S-transferase mu 1IL-8GSTM1KGMeGFPRT-PCRHRPROSInterleukin 8BALFELISAEnzyme-linked immunosorbent assayepidermal growth factorlactate dehydrogenaseLDHBronchoalveolar lavage fluidkeratinocyte basal mediumPhosphate-buffered salinekeratinocyte growth mediumHorseradish peroxidasegreen fluorescent proteinmultiplicity of infectionGlutathione ethyl esterReactive oxygen species
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Authors
Weidong Wu, Vinod Doreswamy, David Diaz-Sanchez, James M. Samet, Matt Kesic, Lisa Dailey, Wenli Zhang, Ilona Jaspers, David B. Peden,