Department of Air Pollution and Noise, Division of Environmental Medicine, Norwegian Institute of Public Health, Oslo, Norway.
Toxicol Lett. 2012 Feb 5;208(3):262-8. doi: 10.1016/j.toxlet.2011.10.025. Epub 2011 Nov 9.
Exposure to diesel engine exhaust particles (DEPs), representing a complex and variable mixture of components, has been associated with lung disease and induction of pro-inflammatory mediators and CYP1A1 expression. The aim of this study was to further characterise DEP-components accounting for these effects. Human bronchial epithelial cells (BEAS-2B) were exposed to either native DEPs, or corresponding methanol DEP-extract or residual DEPs, and investigated with respect to cytotoxicity and expression and release of multiple inflammation-related mediators. Both native DEPs and DEP-extract, but not residual DEPs, induced marked mRNA expression of COX-2, IL-6 and IL-8, as well as cytotoxicity and release of IL-6. However, CYP1A1 was primarily induced by the native and residual DEPs. Overall, the results of near-edge X-ray absorption fine structure (NEXAFS) spectroscopy and gas chromatography with mass spectrometry (GC/MS) analysis of DEP-extracts indicated that the majority of the analysed PAHs and PAH-derivatives were extracted from the particles, but that certain PAH-derivatives, probably their carboxylic isomers, tended to be retained on the residual DEPs. Moreover, it appeared that certain components of the methanol extract may suppress CYP1A1 expression. These results provide insight into how different components of the complex DEP-mixture may be differently involved in DEP-induced pro-inflammatory responses and underscore the importance of identifying and clarifying the roles of active DEP-components in relation to different biological effects.
柴油机排气颗粒(DEP)暴露,代表了成分复杂且多变的混合物,与肺部疾病以及促炎介质和 CYP1A1 表达的诱导有关。本研究的目的是进一步阐明导致这些效应的 DEP 成分。将人支气管上皮细胞(BEAS-2B)暴露于天然 DEP、相应的甲醇 DEP 提取物或残留 DEP,并研究它们对细胞毒性以及多种炎症相关介质的表达和释放的影响。天然 DEP 和 DEP 提取物均能诱导 COX-2、IL-6 和 IL-8 的 mRNA 表达、细胞毒性以及 IL-6 的释放,但残留 DEP 则不能。然而,CYP1A1 主要由天然和残留的 DEP 诱导。总体而言,DEP 提取物的近边 X 射线吸收精细结构(NEXAFS)光谱和气相色谱-质谱(GC/MS)分析结果表明,分析的多环芳烃和多环芳烃衍生物中的大多数已从颗粒中提取出来,但某些多环芳烃衍生物,可能是它们的羧酸异构体,往往残留在残留的 DEP 上。此外,甲醇提取物的某些成分似乎可能抑制 CYP1A1 的表达。这些结果提供了深入了解复杂的 DEP 混合物的不同成分如何参与 DEP 诱导的促炎反应的信息,并强调了识别和阐明与不同生物学效应相关的活性 DEP 成分的重要性。