Endothelial responses of the alveolar barrier in vitro in a dose-controlled exposure to diesel exhaust particulate matter.
Endothelial responses of the alveolar barrier in vitro in a dose-controlled exposure to diesel exhaust particulate matter.
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DOI：
10.1186/s12989-017-0186-4
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发表时间：
2017-03-06
影响因子：
10
通讯作者：
Gutleb AC
中科院分区：
文献类型：
--
作者：
Klein SG;Cambier S;Hennen J;Legay S;Serchi T;Nelissen I;Chary A;Moschini E;Krein A;Blömeke B;Gutleb AC
在过去的250年中，西方国家燃烧产生的颗粒物暴露水平急剧上升，导致环境空气中颗粒物负荷增加。在环境颗粒物中，柴油机排气颗粒物（DEPM）因其普遍存在和对人体健康的影响而起着特殊的作用。近年来，人们认识到空气污染与动脉粥样硬化进展之间可能存在联系。DEPM的中心作用是其对内皮的影响，尤其是对肺泡屏障的影响。在本研究中，一个复杂的三维tetraculture模型的肺泡屏障中使用的剂量控制的暴露方案与现实剂量的DEPM研究内皮细胞的反应。在气-液界面处将培养物暴露于不同剂量的DEPM（SRM 2975）。DEPM暴露不会导致内皮炎症相关标志物（如ICAM-1或E-选择素）的mRNA表达。此外，我们既没有观察到与抗氧化防御相关的基因（如HMOX 1或SOD 1）的表达水平发生显著变化，也没有观察到促炎第二信使（如IL-6或IL-8）的释放。然而，DEPM暴露导致强烈的核转位的转录因子Nrf 2和显着改变的表达CYP 1A 1 mRNA的内皮细胞的四培养。在本研究中，我们证明了使用一个复杂的三维tetraculture系统连同一个国家的最先进的气溶胶暴露设备，研究在体内相关剂量的DEPM对内皮细胞在体外的影响。据我们所知，这项研究是第一个集中在间接影响DEPM对肺泡屏障内皮细胞在体外。暴露于DEPM导致内皮细胞中转录因子Nrf 2的显著激活和核转位。相当低剂量的DEPM具有低但可测量的影响，这与体内研究的最新数据一致。本文的在线版本（doi：10.1186/s12989-017-0186-4）包含补充材料，可供授权用户使用。
During the last 250 years, the level of exposure to combustion-derived particles raised dramatically in western countries, leading to increased particle loads in the ambient air. Among the environmental particles, diesel exhaust particulate matter (DEPM) plays a special role because of its omnipresence and reported effects on human health. During recent years, a possible link between air pollution and the progression of atherosclerosis is recognized. A central effect of DEPM is their impact on the endothelium, especially of the alveolar barrier. In the present study, a complex 3D tetraculture model of the alveolar barrier was used in a dose-controlled exposure scenario with realistic doses of DEPM to study the response of endothelial cells. Tetracultures were exposed to different doses of DEPM (SRM2975) at the air-liquid-interface. DEPM exposure did not lead to the mRNA expression of relevant markers for endothelial inflammation such as ICAM-1 or E-selectin. In addition, we observed neither a significant change in the expression levels of the genes relevant for antioxidant defense, such as HMOX1 or SOD1, nor the release of pro-inflammatory second messengers, such as IL-6 or IL-8. However, DEPM exposure led to strong nuclear translocation of the transcription factor Nrf2 and significantly altered expression of CYP1A1 mRNA in the endothelial cells of the tetraculture. In the present study, we demonstrated the use of a complex 3D tetraculture system together with a state-of-the-art aerosol exposure equipment to study the effects of in vivo relevant doses of DEPM on endothelial cells in vitro. To the best of our knowledge, this study is the first that focuses on indirect effects of DEPM on endothelial cells of the alveolar barrier in vitro. Exposure to DEPM led to significant activation and nuclear translocation of the transcription factor Nrf2 in endothelial cells. The considerably low doses of DEPM had a low but measurable effect, which is in line with recent data from in vivo studies. The online version of this article (doi:10.1186/s12989-017-0186-4) contains supplementary material, which is available to authorized users.