Benzene-extracted components are important for the major activity of diesel exhaust particles - Effect on interleukin-8 gene expression in human bronchial epithelial cells

Epidemiologic and experimental studies suggest that diesel exhaust particle s (DEPs) may be related to increasing respiratory mortality and morbidity, We have shown that DEPs augmented the production of inflammatory cytokines by human airway epithelial cells in vitro. To better understand the mechani sms of their proinflammatory activities, we studied the effects of several components extracted from DEPs on interleukin (IL)-8 expression in human br onchial epithelial cell line BEAS-2B and normal human airway epithelial cel ls obtained from very peripheral airways by an ultrathin bronchoscope. We u sed several agents active on signal transduction pathways in cytokine expre ssion, such as the protein kinase C inhibitor staurosporin, antioxidant age nts including N-acetyl cysteine (NAC) and pyrrolidine dithiocarbamate (PDTC ), and p38 mitogen-activated protein kinase (MAPK) inhibitor SB203580. Benz ene-extracted components showed effects mimicking DEPs on IL-8 gene express ion, release of several cytokines (IL-8; granulocyte macrophage colony-stim ulating factor and regulated on activation, normal T cells expressed and se creted) and nuclear factor (NF)-kappaB activation. We also found that NAG, PDTC, and SB203580 suppressed the activities of DEPs and their benzene extr acts, suggesting the roles of oxidants-mediated NF-KB activation and p38MAP K pathways. Finally, benzo[a]pyrene, one of the important compounds include d in the benzene component, replicated the activities shown by DEPs.