Am. J. Respir. Cell Mol. Biol., Volume 24, Number 4, April, 2001 419-426

Benzene-Extracted Components Are Important for the Major Activity of Diesel Exhaust Particles
Effect on Interleukin-8 Gene Expression in Human Bronchial Epithelial Cells

Shin Kawasaki, Hajime Takizawa, Kazutaka Takami, Masashi Desaki, Hitoshi Okazaki, Tsuyoshi Kasama, Kazuo Kobayashi, Kazuhiko Yamamoto, Kazuhiko Nakahara, Mitsuru Tanaka, Masaru Sagai, and Takayuki Ohtoshi

Departments of Respiratory Medicine and Laboratory Medicine, Graduate School of Medicine, University of Tokyo; First Department of Internal Medicine, School of Medicine, Showa University; WHO Collaborating Centre, Tokyo Medical College, Tokyo; Department of Microbiology, Osaka City Medical University, Osaka; and Faculty of Health Sciences, Aomori University of Health and Welfare, Aomori, Japan

Epidemiologic and experimental studies suggest that diesel exhaust particles (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 mechanisms of their proinflammatory activities, we studied the effects of several components extracted from DEPs on interleukin (IL)-8 expression in human bronchial epithelial cell line BEAS-2B and normal human airway epithelial cells obtained from very peripheral airways by an ultrathin bronchoscope. We used several agents active on signal transduction pathways in cytokine expression, such as the protein kinase C inhibitor staurosporin, antioxidant agents including N-acetyl cysteine (NAC) and pyrrolidine dithiocarbamate (PDTC), and p38 mitogen-activated protein kinase (MAPK) inhibitor SB203580. Benzene-extracted components showed effects mimicking DEPs on IL-8 gene expression, release of several cytokines (IL-8; granulocyte macrophage colony-stimulating factor; and regulated on activation, normal T cells expressed and secreted) and nuclear factor (NF)-B activation. We also found that NAC, PDTC, and SB203580 suppressed the activities of DEPs and their benzene extracts, suggesting the roles of oxidants-mediated NF-B activation and p38MAPK pathways. Finally, benzo[a]pyrene, one of the important compounds included in the benzene component, replicated the activities shown by DEPs.

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