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GSTM1 modulation of IL-8 expression in human epithelial cells exposed to ozone
Citation:
Wu, W., V. Doreswamy, D. Diaz-Sanchez, J. Samet, M. Kesisc, L. Dailey, W. Zhang, I. Jaspers, AND D. Peden. GSTM1 modulation of IL-8 expression in human epithelial cells exposed to ozone. Free Radical Biology and Medicine. Elsevier Science Ltd, New York, NY, 51(2):522-529, (2011).
Impact/Purpose:
THIS MANUSCRIPT WAS ORGINALLY CLEARED VIA PAPER PACKAGE EPHD-12-056 AND ENTERED IN THE SCIENCE INVENTORY
Description:
Exposure to the major air pollutant ozone can aggravate asthma and other lung diseases. Our recent study in humanvolunteers hasshown that the glutathione S-transferase Mu 1(GSTMI)-null genotype is associated with increased airway neutrophilic inflammation induced by inhaled ozone. The aim of this study was to examine the effect of GSTMI modulation on interleukin S (lL-8) production in ozone-exposed human bronchial epithelial cells (BEAS-2B)and the underlying mechanisms. Exposureof BEAS-2B cells to 0.4ppm 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-KB activation. Pharmacological inhibition of NF-KB activation or mutation of the IL-8 promoter at the KB-binding site significantly blocked ozone-induced IL-8 production or IL-8 transcriptional activity, respectively. Knockdown of GSTMI in BEAS-2B cells enhanced ozone-induced NF-KB activationand 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-KB activation, and IL-8 production. Taken together. GSTMI deficiency enhances ozone-induced IL8 production, which is mediated by generated ROS and subsequent NF-KB activation in human bronchial epithelial cells.