Title
Molecular signature of asthma-enhanced sensitivity to cuo nanoparticle aerosols from 3d cell modell
Author
Kooter, I.M.
Ilves, M.
Grollers-Mulderij, M.
Duistermaat, E.
Tromp, P.C.
Kuper, F.
Kinaret, P.
Savolainen, K.
Greco, D.
Karisola, P.
Ndika, J.
Alenius, H.
Publication year
2019
Abstract
More than 5% of any population suffers from asthma, and there are indications that these individuals are more sensitive to nanoparticle aerosols than the healthy population. We used an air–liquid interface model of inhalation exposure to investigate global transcriptomic responses in reconstituted three-dimensional airway epithelia of healthy and asthmatic subjects exposed to pristine (nCuO) and carboxylated (nCuOCOOH) copper oxide nanoparticle aerosols. A dose-dependent increase in cytotoxicity (highest in asthmatic donor cells) and pro-inflammatory signaling within 24 h confirmed the reliability and sensitivity of the system to detect acute inhalation toxicity. Gene expression changes between nanoparticle-exposed versus air-exposed cells were investigated. Hierarchical clustering based on the expression profiles of all differentially expressed genes (DEGs), cell-death-associated DEGs (567 genes), or a subset of 48 highly overlapping DEGs categorized all samples according to “exposure severity”, wherein nanoparticle surface chemistry and asthma are incorporated into the dose–response axis. For example, asthmatics exposed to low and medium dose nCuO clustered with healthy donor cells exposed to medium and high dose nCuO, respectively. Of note, a set of genes with high relevance to mucociliary clearance were observed to distinctly differentiate asthmatic and healthy donor cells. These genes also responded differently to nCuO and nCuOCOOH nanoparticles. Additionally, because response to transition-metal nanoparticles was a highly enriched Gene Ontology term (FDR 8 × 10–13) from the subset of 48 highly overlapping DEGs, these genes may represent biomarkers to a potentially large variety of metal/metal oxide nanoparticles.
Subject
Environment & Sustainability
Urbanisation
Copper(II) oxide
Nanoparticles
Asthma
3d human bronchial epithelial cells
Air−liquid interface and transcriptomics
To reference this document use:
http://resolver.tudelft.nl/uuid:cd24e415-abec-4fdd-ae11-d62a2d05f424
TNO identifier
867537
Source
ACS Nano, 1-15
Document type
article