IUF - Leibniz-Research Institute for Environmental Medicine, Auf'm Hennekamp 50, 40225, Duesseldorf, Germany.
IUTA - Institut für Energie- und Umwelttechnik e.V., Duisburg, Germany.
Sci Rep. 2022 Aug 22;12(1):14255. doi: 10.1038/s41598-022-18098-8.
Cystic fibrosis is an autosomal recessive disorder caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) that can lead to terminal respiratory failure. Ultrafine carbonaceous particles, which are ubiquitous in ambient urban and indoor air, are increasingly considered as major contributors to the global health burden of air pollution. However, their effects on the expression of CFTR and associated genes in lung epithelial cells have not yet been investigated. We therefore evaluated the effects of carbon nanoparticles (CNP), generated by spark-ablation, on the human bronchial epithelial cell line 16HBE14o- at air-liquid interface (ALI) culture conditions. The ALI-cultured cells exhibited epithelial barrier integrity and increased CFTR expression. Following a 4-h exposure to CNP, the cells exhibited a decreased barrier integrity, as well as decreased expression of CFTR transcript and protein levels. Furthermore, transcriptomic analysis revealed that the CNP-exposed cells showed signs of oxidative stress, apoptosis and DNA damage. In conclusion, this study describes spark-ablated carbon nanoparticles in a realistic exposure of aerosols to decrease CFTR expression accompanied by transcriptomic signs of oxidative stress, apoptosis and DNA damage.
囊性纤维化是一种常染色体隐性遗传病，由囊性纤维化跨膜电导调节因子 (CFTR) 的突变引起，可导致终末期呼吸衰竭。超细碳质颗粒广泛存在于环境城市和室内空气中，它们被认为是导致空气污染对全球健康造成负担的主要因素之一。然而，它们对肺上皮细胞中 CFTR 及其相关基因表达的影响尚未得到研究。因此，我们评估了由火花烧蚀产生的碳纳米颗粒 (CNP) 在气液界面 (ALI) 培养条件下对人支气管上皮细胞系 16HBE14o- 的影响。在 ALI 培养的细胞中，上皮屏障完整性增加，CFTR 表达增加。在暴露于 CNP 4 小时后，细胞的屏障完整性降低，CFTR 转录本和蛋白水平的表达也降低。此外，转录组分析显示，暴露于 CNP 的细胞表现出氧化应激、细胞凋亡和 DNA 损伤的迹象。总之，本研究描述了在气溶胶的实际暴露中，火花烧蚀的碳纳米颗粒会降低 CFTR 的表达，同时伴有氧化应激、细胞凋亡和 DNA 损伤的转录组迹象。
