Air pollution particles induce IL-6 gene expression in human airway epithelial cells via NF-κB activation
Air pollution particles induce IL-6 gene expression in human airway epithelial cells via NF-κB activation
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DOI：
10.1165/ajrcmb.19.1.3132
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发表时间：
1998-07-01
影响因子：
6.4
通讯作者：
Devlin, RB
中科院分区：
文献类型：
--
作者：
Quay, JL;Reed, W;Devlin, RB
空气中的细颗粒物与死亡率和发病率的增加有关。颗粒空气污染是一种复杂的混合物，因地区而异，包括许多成分，包括残油飞灰（ROFA），一种发电厂和工业燃油燃烧的副产品。暴露于ROFA的人气道上皮细胞释放炎性细胞因子，包括白细胞介素(IL)-6、IL-8和肿瘤坏死因子。这些基因的表达依赖于顺式调控元件的转录前结合，包括核因子κ B （nf - κ B）。为了研究NF-kappa B在颗粒诱导的IL-6应答中的作用，我们在体外将人气道上皮细胞（BEAS-2B）暴露于ROFA。ROFA刺激了IL-6信使RNA (mRNA)I的时间和剂量依赖性增加，在此之前，与IL-6启动子中nf - κ B序列基序结合的核蛋白被激活。瞬时转染带有与荧光素酶报告基因相连的IL-6基因5'启动子区域的BEAS-2B细胞证实，NF-kappa B结合是IL-6 mRNA转录所必需的。IL-6反应被金属螯合剂去铁胺和自由基清除剂n -乙酰- l-半胱氨酸抑制，提示NF-kappa B的活化可能是通过ROFA中发现的过渡金属产生的活性氧中间体介导的。因此，NF-kappa B的激活可能是暴露于石油燃烧产生的颗粒后炎症级联反应的关键第一步。
Fine particles in the air have been associated with increased mortality and morbidity. Particulate air pollution is a complex mixture which varies by region and includes a number of components including residual oil fly ash (ROFA), a byproduct of power plant and industry fuel-oil combustion. Human airway epithelial cells exposed to ROFA release inflammatory cytokines including interleukin (IL)-6, IL-8, and tumor necrosis factor. Expression of these genes is dependent upon pretranscriptional binding of cis regulatory elements, including nuclear factor kappa B (NF-kappa B). To investigate the role of NF-kappa B in the particulate-induced IL-6 response, we exposed human airway epithelial cells (BEAS-2B) to ROFA in vitro. ROFA stimulated a time- and dose-dependent increase in IL-6 messenger RNA (mRNA)I which was preceded by the activation of nuclear proteins binding to the NF-kappa B sequence motif in the IL-6 promoter. Transient transfection of BEAS-2B cells with the 5' promoter region of the IL-6 gene linked to a luciferase reporter gene confirmed that NF-kappa B binding is necessary for the transcription of IL-6 mRNA. The IL-6 response was inhibited by the metal chelator deferoxamine and the free radical scavenger N-acetyl-L-cysteine, suggesting that the activation of NF-kappa B may be mediated through reactive oxygen intermediates generated by transition metals found in ROFA. Activation of NF-kappa B may therefore be a critical first step in the inflammatory cascade following exposure to particles generated by oil combustion.