The diesel exhaust component pyrene induces expression of IL-8 but not of eotaxin
The diesel exhaust component pyrene induces expression of IL-8 but not of eotaxin
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DOI：
10.1016/s1567-5769(03)00135-8
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发表时间：
2003-10-01
影响因子：
5.6
通讯作者：
Duschl, A
中科院分区：
文献类型：
--
作者：
Bömmel, H;Haake, M;Duschl, A
环境污染物可以影响免疫调节分子的表达，并通过这种方式促进过敏。致炎趋化因子的局部合成是过敏性气道炎症发生发展的一个重要方面。我们研究了在柴油车尾气颗粒物(DEP)中含有的一种多环芳烃(PAH)--芘对趋化因子白介素8(IL-8)和嗜酸性粒细胞趋化因子(Eoaxin)转录和分泌的影响。在人成纤维细胞系A549和HeLa中检测各自启动子控制下的报告基因，检测A549细胞的mRNA产量和原代人成纤维细胞培养上清液中的蛋白质产量。用高效液相色谱法测定细胞培养上清液中的芘含量。芘可增加IL-8的启动子活性，增加IL-8的mRNA和蛋白表达。报告基因研究中的激活效应通过突变IL-8启动子中的一个NF-kappaB或AP-1结合位点而被取消。相反，尽管嗜酸性粒细胞趋化因子在哮喘中起重要作用，但芘对嗜酸性粒细胞趋化蛋白启动子的转录没有影响。我们的数据显示，芘对趋化因子的合成有特定的影响，这并不局限于主要与特应性疾病相关的介质。芘也会影响不是来自肺组织的细胞，这表明对这种污染物有更广泛的免疫调节影响。(C)2003爱思唯尔B.V.保留所有权利。
Environmental pollutants can influence the expression of immunoregulatory molecules and, in this way, promote allergies. The local synthesis of proinflammatory chemokines is an important aspect in the development of allergic airway inflammation. We have characterized the influence of pyrene, a polycyclic aromatic hydrocarbon (PAH) contained, for example, in diesel exhaust particles (DEP), on transcription and secretion of the chemokines interleukin-8 (IL-8) and eotaxin. Reporter genes under control of the respective promoters were tested in the human cell lines A549 and HeLa, mRNA production was assayed in A549 cells and protein production was measured by ELISA in cell supernatants from primary human fibroblasts. Pyrene content of cell supernatants was measured by analytical HPLC. Promoter activity, mRNA production and protein expression of IL-8 were increased by pyrene. The activating effect in reporter gene studies was abolished by mutating either an NF-kappaB or an AP-1 binding site in the IL-8 promoter. In contrast, pyrene showed no effect on transcription from the eotaxin promoter, despite the important role of this chemokine in asthma. Our data show that pyrene has specific effects on chemokine synthesis, which are not restricted to mediators primarily associated with atopic diseases. Pyrene also affected cells not derived from lung tissue, which suggests a broader immunoregulatory influence for this pollutant. (C) 2003 Elsevier B.V. All rights reserved.