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Human airway construct model is suitable for studying transcriptome changes associated with indoor air particulate matter toxicity.
Indoor Air ( IF 4.3 ) Pub Date : 2020-01-23 , DOI: 10.1111/ina.12637
Maria-Elisa Nordberg 1 , Martin Täubel 2 , Pasi I Jalava 1 , Kelly BéruBé 3 , Arja Tervahauta 1 , Anne Hyvärinen 2 , Kati Huttunen 1
Affiliation  

In vitro models mimicking the human respiratory system are essential when investigating the toxicological effects of inhaled indoor air particulate matter (PM). We present a pulmonary cell culture model for studying indoor air PM toxicity. We exposed normal human bronchial epithelial cells, grown on semi‐permeable cell culture membranes, to four doses of indoor air PM in the air‐liquid interface. We analyzed the chemokine interleukin‐8 concentration from the cell culture medium, protein concentration from the apical wash, measured tissue electrical resistance, and imaged airway constructs using light and transmission electron microscopy. We sequenced RNA using a targeted RNA toxicology panel for 386 genes associated with toxicological responses. PM was collected from a non‐complaint residential environment over 1 week. Sample collection was concomitant with monitoring size‐segregated PM counts and determination of microbial levels and diversity. PM exposure was not acutely toxic for the cells, and we observed up‐regulation of 34 genes and down‐regulation of 17 genes when compared to blank sampler control exposure. The five most up‐regulated genes were related to immunotoxicity. Despite indications of incomplete cell differentiation, this model enabled the comparison of a toxicological transcriptome associated with indoor air PM exposure.

中文翻译:

人气道构建模型适用于研究与室内空气颗粒物毒性相关的转录组变化。

在调查吸入的室内空气颗粒物(PM)的毒理学影响时,模仿人体呼吸系统的体外模型至关重要。我们提出了一种用于研究室内空气PM毒性的肺细胞培养模型。我们将生长在半透性细胞培养膜上的正常人支气管上皮细胞暴露于气液界面中的四剂室内空气PM中。我们分析了细胞培养基中趋化因子白细胞介素8的浓度,根尖洗液中的蛋白质浓度,测量的组织电阻以及使用光和透射电镜对成像的气道结构进行了成像。我们使用靶向RNA毒理学小组对与毒理学反应相关的386个基因进行了RNA测序。在1周内从无投诉的居住环境中收集了PM。样品收集伴随着监测大小分离的PM计数以及确定微生物水平和多样性。PM暴露对细胞没有急性毒性,与空白样品对照暴露相比,我们观察到34个基因的上调和17个基因的下调。五个最上调的基因与免疫毒性有关。尽管有迹象表明细胞分化不完全,但是该模型能够比较与室内空气中PM暴露相关的毒理学转录组。五个最上调的基因与免疫毒性有关。尽管有迹象表明细胞分化不完全,但是该模型能够比较与室内空气中PM暴露相关的毒理学转录组。五个最上调的基因与免疫毒性有关。尽管有迹象表明细胞分化不完全,但是该模型能够比较与室内空气中PM暴露相关的毒理学转录组。
更新日期:2020-01-23
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