Work Environment Toxicology, Institute of Environmental Medicine, Karolinska Institutet, Box 210, Stockholm, SE-171 77, Sweden.
Lung and Airway Research, Institute of Environmental Medicine, Karolinska Institutet, Box 210, Stockholm SE-171 77, Sweden.
Toxicol In Vitro. 2018 Feb;46:219-228. doi: 10.1016/j.tiv.2017.09.016. Epub 2017 Sep 22.
The cytotoxicity of aldehydes was studied using human primary bronchial epithelial cells (PBEC) cultured at the air-liquid interface (ALI) or under submerged conditions. PBEC were exposed for 30min via the air phase to acrolein (0.1-1mg/m), crotonaldehyde (1.5-15mg/m) or hexanal (22-221mg/m) or under submerged conditions to acrolein (0.1 and 0.2mg/L), crotonaldehyde (1 and 2mg/L) or hexanal (10 and 20mg/L). Cell culture medium was collected 8h and 24h post-exposure and analyzed for interleukin-8 (IL-8) and matrix metalloprotein-9 (MMP-9). The gene expression of inflammatory and oxidative stress markers were measured 6h post-exposure. In the ALI setup, all three aldehydes caused increased secretion of IL-8, acrolein and crotonaldehyde also increased the gene expression of inflammatory and oxidative stress markers. In contrast, exposure under submerged conditions resulted in significantly reduced IL-8 secretion. The inflammatory response seen in the air phase exposures correspond well with previous in vivo studies. This indicates that lung models cultured at ALI are more suitable than submerged cell cultures in toxicity assessment studies of inhaled agents.
采用在气液界面（ALI）或浸没条件下培养的人原代支气管上皮细胞（PBEC）研究了醛的细胞毒性。通过空气相将 PBEC 暴露于丙烯醛（0.1-1mg/m）、巴豆醛（1.5-15mg/m）或己醛（22-221mg/m）30min，或在浸没条件下将 PBEC 暴露于丙烯醛（0.1 和 0.2mg/L）、巴豆醛（1 和 2mg/L）或己醛（10 和 20mg/L）。暴露后 8h 和 24h 收集细胞培养物培养基，并分析白细胞介素-8（IL-8）和基质金属蛋白酶-9（MMP-9）。暴露后 6h 测量炎症和氧化应激标志物的基因表达。在 ALI 装置中，三种醛都导致 IL-8 的分泌增加，丙烯醛和巴豆醛还增加了炎症和氧化应激标志物的基因表达。相比之下，在浸没条件下的暴露导致 IL-8 分泌显著减少。空气相暴露中观察到的炎症反应与先前的体内研究非常吻合。这表明在毒性评估研究中，在 ALI 培养的肺模型比浸没细胞培养更适合用于吸入剂。
