Benzene-extracted components are important for the major activity of diesel exhaust particles - Effect on interleukin-8 gene expression in human bronchial epithelial cells
Benzene-extracted components are important for the major activity of diesel exhaust particles - Effect on interleukin-8 gene expression in human bronchial epithelial cells
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DOI：
10.1165/ajrcmb.24.4.4085
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发表时间：
2001-04-01
影响因子：
6.4
通讯作者：
Ohtoshi, T
中科院分区：
文献类型：
--
作者：
Kawasaki, S;Takizawa, H;Ohtoshi, T
流行病学和实验研究表明，柴油废气颗粒（DEPs）可能与呼吸道死亡率和发病率的增加有关。我们已经在体外证明，DEPs增加了人气道上皮细胞炎症细胞因子的产生。为了更好地了解其促炎活性的机制，我们研究了从DEPs中提取的几种成分对人支气管上皮细胞系BEAS-2B和通过超薄支气管镜从非常外周气道获得的正常人气道上皮细胞中白细胞介素(IL)-8表达的影响。我们使用了几种活跃于细胞因子表达信号转导途径的药物，如蛋白激酶C抑制剂staurosporin，抗氧化剂包括n-乙酰半胱氨酸（NAC）和吡咯烷二硫代氨基甲酸酯（PDTC），以及p38丝裂原活化蛋白激酶（MAPK）抑制剂SB203580。苯提取成分对IL-8基因表达、多种细胞因子（IL-8、粒细胞巨噬细胞集落刺激因子及调节活化、正常T细胞表达和分泌）和核因子(NF)-kappaB活化具有模拟DEPs的作用。我们还发现NAG、PDTC和SB203580抑制DEPs及其苯提取物的活性，提示氧化剂介导的NF-KB激活和p38MAPK通路的作用。最后，苯并[a]芘，苯组分中包含的重要化合物之一，复制了dep所显示的活性。
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)-kappaB activation. We also found that NAG, PDTC, and SB203580 suppressed the activities of DEPs and their benzene extracts, suggesting the roles of oxidants-mediated NF-KB activation and p38MAPK pathways. Finally, benzo[a]pyrene, one of the important compounds included in the benzene component, replicated the activities shown by DEPs.