GSTM1 modulation of IL-8 expression in human bronchial epithelial cells exposed to ozone.

GSTM1 modulation of IL-8 expression in human bronchial epithelial cells exposed to ozone.
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DOI:
10.1016/j.freeradbiomed.2011.05.006
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发表时间:
2011-07-15
影响因子:
7.4
通讯作者:
Peden, David B.
Peden, David B.
中科院分区:
医学1区
文献类型:
--
作者:
Wu, Weidong;Doreswamy, Vinod;Diaz-Sanchez, David;Samet, James M.;Kesic, Matt;Dailey, Lisa;Zhang, Wenli;Jaspers, Ilona;Peden, David B.

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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 NFκB activation. Pharmacological inhibition of NFκB activation or mutation of IL-8 promoter at 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 NFκB activation and IL-8 production. Consistently, 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, NFκB activation and IL-8 production. Taken together, GSTM1 deficiency enhances ozone-induced IL-8 production, which is mediated by generated ROS and subsequent NFκB activation in human bronchial epithelial cells.
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