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Cerium oxide and barium sulfate nanoparticle inhalation affects gene expression in alveolar epithelial cells type II

BACKGROUND: Understanding the molecular mechanisms of nanomaterial interacting with cellular systems is important for appropriate risk assessment. The identification of early biomarkers for potential (sub-)chronic effects of nanoparticles provides a promising approach towards cost-intensive and anim...

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Autores principales: Schwotzer, Daniela, Niehof, Monika, Schaudien, Dirk, Kock, Heiko, Hansen, Tanja, Dasenbrock, Clemens, Creutzenberg, Otto
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5819288/
https://www.ncbi.nlm.nih.gov/pubmed/29463257
http://dx.doi.org/10.1186/s12951-018-0343-4
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author Schwotzer, Daniela
Niehof, Monika
Schaudien, Dirk
Kock, Heiko
Hansen, Tanja
Dasenbrock, Clemens
Creutzenberg, Otto
author_facet Schwotzer, Daniela
Niehof, Monika
Schaudien, Dirk
Kock, Heiko
Hansen, Tanja
Dasenbrock, Clemens
Creutzenberg, Otto
author_sort Schwotzer, Daniela
collection PubMed
description BACKGROUND: Understanding the molecular mechanisms of nanomaterial interacting with cellular systems is important for appropriate risk assessment. The identification of early biomarkers for potential (sub-)chronic effects of nanoparticles provides a promising approach towards cost-intensive and animal consuming long-term studies. As part of a 90-day inhalation toxicity study with CeO(2) NM-212 and BaSO(4) NM-220 the present investigations on gene expression and immunohistochemistry should reveal details on underlying mechanisms of pulmonary effects. The role of alveolar epithelial cells type II (AEII cells) is focused since its contribution to defense against inhaled particles and potentially resulting adverse effects is assumed. Low dose levels should help to specify particle-related events, including inflammation and oxidative stress. RESULTS: Rats were exposed to clean air, 0.1, 0.3, 1.0, and 3.0 mg/m(3) CeO(2) NM-212 or 50.0 mg/m(3) BaSO(4) NM-220 and the expression of 391 genes was analyzed in AEII cells after one, 28 and 90 days exposure. A total number of 34 genes was regulated, most of them related to inflammatory mediators. Marked changes in gene expression were measured for Ccl2, Ccl7, Ccl17, Ccl22, Ccl3, Ccl4, Il-1α, Il-1ß, and Il-1rn (inflammation), Lpo and Noxo1 (oxidative stress), and Mmp12 (inflammation/lung cancer). Genes related to genotoxicity and apoptosis did not display marked regulation. Although gene expression was less affected by BaSO(4) compared to CeO(2) the gene pattern showed great overlap. Gene expression was further analyzed in liver and kidney tissue showing inflammatory responses in both organs and marked downregulation of oxidative stress related genes in the kidney. Increases in the amount of Ce were measured in liver but not in kidney tissue. Investigation of selected genes on protein level revealed increased Ccl2 in bronchoalveolar lavage of exposed animals and increased Lpo and Mmp12 in the alveolar epithelia. CONCLUSION: AEII cells contribute to CeO(2) nanoparticle caused inflammatory and oxidative stress reactions in the respiratory tract by the release of related mediators. Effects of BaSO(4) exposure are low. However, overlap between both substances were detected and support identification of potential early biomarkers for nanoparticle effects on the respiratory system. Signs for long-term effects need to be further evaluated by comparison to a respective exposure setting. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12951-018-0343-4) contains supplementary material, which is available to authorized users.
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spelling pubmed-58192882018-02-21 Cerium oxide and barium sulfate nanoparticle inhalation affects gene expression in alveolar epithelial cells type II Schwotzer, Daniela Niehof, Monika Schaudien, Dirk Kock, Heiko Hansen, Tanja Dasenbrock, Clemens Creutzenberg, Otto J Nanobiotechnology Research BACKGROUND: Understanding the molecular mechanisms of nanomaterial interacting with cellular systems is important for appropriate risk assessment. The identification of early biomarkers for potential (sub-)chronic effects of nanoparticles provides a promising approach towards cost-intensive and animal consuming long-term studies. As part of a 90-day inhalation toxicity study with CeO(2) NM-212 and BaSO(4) NM-220 the present investigations on gene expression and immunohistochemistry should reveal details on underlying mechanisms of pulmonary effects. The role of alveolar epithelial cells type II (AEII cells) is focused since its contribution to defense against inhaled particles and potentially resulting adverse effects is assumed. Low dose levels should help to specify particle-related events, including inflammation and oxidative stress. RESULTS: Rats were exposed to clean air, 0.1, 0.3, 1.0, and 3.0 mg/m(3) CeO(2) NM-212 or 50.0 mg/m(3) BaSO(4) NM-220 and the expression of 391 genes was analyzed in AEII cells after one, 28 and 90 days exposure. A total number of 34 genes was regulated, most of them related to inflammatory mediators. Marked changes in gene expression were measured for Ccl2, Ccl7, Ccl17, Ccl22, Ccl3, Ccl4, Il-1α, Il-1ß, and Il-1rn (inflammation), Lpo and Noxo1 (oxidative stress), and Mmp12 (inflammation/lung cancer). Genes related to genotoxicity and apoptosis did not display marked regulation. Although gene expression was less affected by BaSO(4) compared to CeO(2) the gene pattern showed great overlap. Gene expression was further analyzed in liver and kidney tissue showing inflammatory responses in both organs and marked downregulation of oxidative stress related genes in the kidney. Increases in the amount of Ce were measured in liver but not in kidney tissue. Investigation of selected genes on protein level revealed increased Ccl2 in bronchoalveolar lavage of exposed animals and increased Lpo and Mmp12 in the alveolar epithelia. CONCLUSION: AEII cells contribute to CeO(2) nanoparticle caused inflammatory and oxidative stress reactions in the respiratory tract by the release of related mediators. Effects of BaSO(4) exposure are low. However, overlap between both substances were detected and support identification of potential early biomarkers for nanoparticle effects on the respiratory system. Signs for long-term effects need to be further evaluated by comparison to a respective exposure setting. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12951-018-0343-4) contains supplementary material, which is available to authorized users. BioMed Central 2018-02-20 /pmc/articles/PMC5819288/ /pubmed/29463257 http://dx.doi.org/10.1186/s12951-018-0343-4 Text en © The Author(s) 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Schwotzer, Daniela
Niehof, Monika
Schaudien, Dirk
Kock, Heiko
Hansen, Tanja
Dasenbrock, Clemens
Creutzenberg, Otto
Cerium oxide and barium sulfate nanoparticle inhalation affects gene expression in alveolar epithelial cells type II
title Cerium oxide and barium sulfate nanoparticle inhalation affects gene expression in alveolar epithelial cells type II
title_full Cerium oxide and barium sulfate nanoparticle inhalation affects gene expression in alveolar epithelial cells type II
title_fullStr Cerium oxide and barium sulfate nanoparticle inhalation affects gene expression in alveolar epithelial cells type II
title_full_unstemmed Cerium oxide and barium sulfate nanoparticle inhalation affects gene expression in alveolar epithelial cells type II
title_short Cerium oxide and barium sulfate nanoparticle inhalation affects gene expression in alveolar epithelial cells type II
title_sort cerium oxide and barium sulfate nanoparticle inhalation affects gene expression in alveolar epithelial cells type ii
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5819288/
https://www.ncbi.nlm.nih.gov/pubmed/29463257
http://dx.doi.org/10.1186/s12951-018-0343-4
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