Flemish Institute for Technological Research (VITO NV), Environmental Risk and Health Unit, Mol, Belgium.
Institut Català de Nanotecnologia (ICN), Barcelona, Spain.
Toxicol Lett. 2014 Aug 4;228(3):157-69. doi: 10.1016/j.toxlet.2014.05.006. Epub 2014 May 10.
Fragmentary knowledge exists on cellular signaling responses underlying possible adverse health effects of CoO- and CeO2-nanoparticles (NP)s after inhalation. We aimed to perform a time kinetic study of gene expression profiles induced by these NPs in alveolar A549 and bronchial BEAS-2B epithelial cells, and investigated possible immune system modulation. The kinetics of the cell responses induced by the NPs were different between the lung epithelial models. Both CoO- and CeO2-NP exposure induced mainly downregulation of gene transcription. BEAS-2B cells were found to be more sensitive, as they showed a higher number of differentially expressed transcripts (DET) at a 10-fold lower NP-concentration than A549 cells. Hierarchical clustering of all DET indicated that the transcriptional responses were heterogeneous among the two cell types and two NPs. Between 1% and 14% DET encoding markers involved in immune processes were observed. The transcriptional impact of the metal oxide NPs appeared to be cell-dependent, both at the general and immune response level, whereas each lung epithelial cell model responded differently to the two NP types. Thus, the study provides gene expression markers and immune processes involved in CoO- and CeO2-NP-induced toxicity, and demonstrates the usefulness of comprehensive-omics studies to differentiate between NP responses.
关于吸入 CoO 和 CeO2 纳米颗粒 (NP) 后可能对健康产生不良影响的细胞信号转导反应,目前只有一些零散的知识。我们旨在对这些 NP 诱导的肺泡 A549 和支气管 BEAS-2B 上皮细胞中的基因表达谱进行时间动力学研究,并研究可能的免疫系统调节。NP 诱导的细胞反应的动力学在肺上皮模型之间有所不同。CoO 和 CeO2-NP 暴露主要诱导基因转录下调。与 A549 细胞相比,BEAS-2B 细胞对 NP 的敏感性更高,因为它们在低 10 倍的 NP 浓度下显示出更多差异表达的转录本 (DET)。所有 DET 的层次聚类表明,两种细胞类型和两种 NP 的转录反应具有异质性。观察到编码参与免疫过程的标志物的 DET 占 1%至 14%。金属氧化物 NP 的转录影响似乎取决于细胞,无论是在一般反应还是免疫反应水平,而每种肺上皮细胞模型对两种 NP 类型的反应都不同。因此,该研究提供了 CoO 和 CeO2-NP 诱导毒性涉及的基因表达标志物和免疫过程,并证明了综合组学研究在区分 NP 反应方面的有用性。