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Molecular Signature of Asthma-Enhanced Sensitivity to CuO Nanoparticle Aerosols from 3D Cell Model
[Image: see text] 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...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American
Chemical Society
2019
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6750904/ https://www.ncbi.nlm.nih.gov/pubmed/31188557 http://dx.doi.org/10.1021/acsnano.9b01823 |
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author | Kooter, Ingeborg Ilves, Marit Gröllers-Mulderij, Mariska Duistermaat, Evert Tromp, Peter C. Kuper, Frieke Kinaret, Pia Savolainen, Kai Greco, Dario Karisola, Piia Ndika, Joseph Alenius, Harri |
author_facet | Kooter, Ingeborg Ilves, Marit Gröllers-Mulderij, Mariska Duistermaat, Evert Tromp, Peter C. Kuper, Frieke Kinaret, Pia Savolainen, Kai Greco, Dario Karisola, Piia Ndika, Joseph Alenius, Harri |
author_sort | Kooter, Ingeborg |
collection | PubMed |
description | [Image: see text] 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 (nCuO(COOH)) 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 nCuO(COOH) 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. |
format | Online Article Text |
id | pubmed-6750904 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | American
Chemical Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-67509042019-09-19 Molecular Signature of Asthma-Enhanced Sensitivity to CuO Nanoparticle Aerosols from 3D Cell Model Kooter, Ingeborg Ilves, Marit Gröllers-Mulderij, Mariska Duistermaat, Evert Tromp, Peter C. Kuper, Frieke Kinaret, Pia Savolainen, Kai Greco, Dario Karisola, Piia Ndika, Joseph Alenius, Harri ACS Nano [Image: see text] 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 (nCuO(COOH)) 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 nCuO(COOH) 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. American Chemical Society 2019-06-12 2019-06-25 /pmc/articles/PMC6750904/ /pubmed/31188557 http://dx.doi.org/10.1021/acsnano.9b01823 Text en Copyright © 2019 American Chemical Society This is an open access article published under a Creative Commons Attribution (CC-BY) License (http://pubs.acs.org/page/policy/authorchoice_ccby_termsofuse.html) , which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited. |
spellingShingle | Kooter, Ingeborg Ilves, Marit Gröllers-Mulderij, Mariska Duistermaat, Evert Tromp, Peter C. Kuper, Frieke Kinaret, Pia Savolainen, Kai Greco, Dario Karisola, Piia Ndika, Joseph Alenius, Harri Molecular Signature of Asthma-Enhanced Sensitivity to CuO Nanoparticle Aerosols from 3D Cell Model |
title | Molecular
Signature of Asthma-Enhanced Sensitivity
to CuO Nanoparticle Aerosols from 3D Cell Model |
title_full | Molecular
Signature of Asthma-Enhanced Sensitivity
to CuO Nanoparticle Aerosols from 3D Cell Model |
title_fullStr | Molecular
Signature of Asthma-Enhanced Sensitivity
to CuO Nanoparticle Aerosols from 3D Cell Model |
title_full_unstemmed | Molecular
Signature of Asthma-Enhanced Sensitivity
to CuO Nanoparticle Aerosols from 3D Cell Model |
title_short | Molecular
Signature of Asthma-Enhanced Sensitivity
to CuO Nanoparticle Aerosols from 3D Cell Model |
title_sort | molecular
signature of asthma-enhanced sensitivity
to cuo nanoparticle aerosols from 3d cell model |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6750904/ https://www.ncbi.nlm.nih.gov/pubmed/31188557 http://dx.doi.org/10.1021/acsnano.9b01823 |
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