Advanced in vitro exposure systems.

Carbon nanoparticles adversely affect CFTR expression and toxicologically relevant pathways

22. Aug. 2022

https://doi.org/10.1038/s41598-022-18098-8

Torben Stermann1, Thach Nguyen1, Burkhard Stahlmecke2, Ana Maria Todea2, Selina Woeste1, Inken Hacheney1, Jean Krutmann1,3, Klaus Unfried1, Roel P. F. Schins1 & Andrea Rossi1
1IUF – Leibniz-Research Institute for Environmental Medicine, Auf’m Hennekamp 50, 40225 Duesseldorf, Germany. 
2IUTA – Institut für Energie- und Umwelttechnik e.V., Duisburg, Germany. 
3Medical Faculty, Heinrich Heine University, Düsseldorf, Germany. *email: andrea.rossi@iuf-duesseldorf.de

 

In the present study the 16HBE14o- cells were exposed in an automated exposure station at air-liquid interface conditions, using the controlled generation of carbon nanoparticles (CNP) aerosols by spark-ablation. This study reports that CNP exposure leads to decrease cystic fibrosis transmembrane conductance regulator (CFTR) expression accompanied by transcriptomic signs of oxidative stress, apoptosis and DNA damage.

 

Abstract

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 CNPexposed 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.

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