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Comprehensive proteome analysis of nasal lavage samples after controlled exposure to welding nanoparticles shows an induced acute phase and a nuclear receptor, LXR/RXR, activation that influence the status of the extracellular matrix

BACKGROUND: Epidemiological studies have shown that many welders experience respiratory symptoms. During the welding process a large number of airborne nanosized particles are generated, which might be inhaled and deposited in the respiratory tract. Knowledge of the underlying mechanisms behind obse...

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Autores principales: Ali, Neserin, Ljunggren, Stefan, Karlsson, Helen M., Wierzbicka, Aneta, Pagels, Joakim, Isaxon, Christina, Gudmundsson, Anders, Rissler, Jenny, Nielsen, Jörn, Lindh, Christian H., Kåredal, Monica
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5946400/
https://www.ncbi.nlm.nih.gov/pubmed/29760600
http://dx.doi.org/10.1186/s12014-018-9196-y
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author Ali, Neserin
Ljunggren, Stefan
Karlsson, Helen M.
Wierzbicka, Aneta
Pagels, Joakim
Isaxon, Christina
Gudmundsson, Anders
Rissler, Jenny
Nielsen, Jörn
Lindh, Christian H.
Kåredal, Monica
author_facet Ali, Neserin
Ljunggren, Stefan
Karlsson, Helen M.
Wierzbicka, Aneta
Pagels, Joakim
Isaxon, Christina
Gudmundsson, Anders
Rissler, Jenny
Nielsen, Jörn
Lindh, Christian H.
Kåredal, Monica
author_sort Ali, Neserin
collection PubMed
description BACKGROUND: Epidemiological studies have shown that many welders experience respiratory symptoms. During the welding process a large number of airborne nanosized particles are generated, which might be inhaled and deposited in the respiratory tract. Knowledge of the underlying mechanisms behind observed symptoms is still partly lacking, although inflammation is suggested to play a central role. The aim of this study was to investigate the effects of welding fume particle exposure on the proteome expression level in welders suffering from respiratory symptoms, and changes in protein mediators in nasal lavage samples were analyzed. Such mediators will be helpful to clarify the pathomechanisms behind welding fume particle-induced effects. METHODS: In an exposure chamber, 11 welders with work-related symptoms in the lower airways during the last month were exposed to mild-steel welding fume particles (1 mg/m(3)) and to filtered air, respectively, in a double-blind manner. Nasal lavage samples were collected before, immediately after, and the day after exposure. The proteins in the nasal lavage were analyzed with two different mass spectrometry approaches, label-free discovery shotgun LC–MS/MS and a targeted selected reaction monitoring LC–MS/MS analyzing 130 proteins and four in vivo peptide degradation products. RESULTS: The analysis revealed 30 significantly changed proteins that were associated with two main pathways; activation of acute phase response signaling and activation of LXR/RXR, which is a nuclear receptor family involved in lipid signaling. Connective tissue proteins and proteins controlling the degradation of such tissues, including two different matrix metalloprotease proteins, MMP8 and MMP9, were among the significantly changed enzymes and were identified as important key players in the pathways. CONCLUSION: Exposure to mild-steel welding fume particles causes measurable changes on the proteome level in nasal lavage matrix in exposed welders, although no clinical symptoms were manifested. The results suggested that the exposure causes an immediate effect on the proteome level involving acute phase proteins and mediators regulating lipid signaling. Proteases involved in maintaining the balance between the formation and degradation of extracellular matrix proteins are important key proteins in the induced effects. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12014-018-9196-y) contains supplementary material, which is available to authorized users.
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spelling pubmed-59464002018-05-14 Comprehensive proteome analysis of nasal lavage samples after controlled exposure to welding nanoparticles shows an induced acute phase and a nuclear receptor, LXR/RXR, activation that influence the status of the extracellular matrix Ali, Neserin Ljunggren, Stefan Karlsson, Helen M. Wierzbicka, Aneta Pagels, Joakim Isaxon, Christina Gudmundsson, Anders Rissler, Jenny Nielsen, Jörn Lindh, Christian H. Kåredal, Monica Clin Proteomics Research BACKGROUND: Epidemiological studies have shown that many welders experience respiratory symptoms. During the welding process a large number of airborne nanosized particles are generated, which might be inhaled and deposited in the respiratory tract. Knowledge of the underlying mechanisms behind observed symptoms is still partly lacking, although inflammation is suggested to play a central role. The aim of this study was to investigate the effects of welding fume particle exposure on the proteome expression level in welders suffering from respiratory symptoms, and changes in protein mediators in nasal lavage samples were analyzed. Such mediators will be helpful to clarify the pathomechanisms behind welding fume particle-induced effects. METHODS: In an exposure chamber, 11 welders with work-related symptoms in the lower airways during the last month were exposed to mild-steel welding fume particles (1 mg/m(3)) and to filtered air, respectively, in a double-blind manner. Nasal lavage samples were collected before, immediately after, and the day after exposure. The proteins in the nasal lavage were analyzed with two different mass spectrometry approaches, label-free discovery shotgun LC–MS/MS and a targeted selected reaction monitoring LC–MS/MS analyzing 130 proteins and four in vivo peptide degradation products. RESULTS: The analysis revealed 30 significantly changed proteins that were associated with two main pathways; activation of acute phase response signaling and activation of LXR/RXR, which is a nuclear receptor family involved in lipid signaling. Connective tissue proteins and proteins controlling the degradation of such tissues, including two different matrix metalloprotease proteins, MMP8 and MMP9, were among the significantly changed enzymes and were identified as important key players in the pathways. CONCLUSION: Exposure to mild-steel welding fume particles causes measurable changes on the proteome level in nasal lavage matrix in exposed welders, although no clinical symptoms were manifested. The results suggested that the exposure causes an immediate effect on the proteome level involving acute phase proteins and mediators regulating lipid signaling. Proteases involved in maintaining the balance between the formation and degradation of extracellular matrix proteins are important key proteins in the induced effects. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12014-018-9196-y) contains supplementary material, which is available to authorized users. BioMed Central 2018-05-11 /pmc/articles/PMC5946400/ /pubmed/29760600 http://dx.doi.org/10.1186/s12014-018-9196-y 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
Ali, Neserin
Ljunggren, Stefan
Karlsson, Helen M.
Wierzbicka, Aneta
Pagels, Joakim
Isaxon, Christina
Gudmundsson, Anders
Rissler, Jenny
Nielsen, Jörn
Lindh, Christian H.
Kåredal, Monica
Comprehensive proteome analysis of nasal lavage samples after controlled exposure to welding nanoparticles shows an induced acute phase and a nuclear receptor, LXR/RXR, activation that influence the status of the extracellular matrix
title Comprehensive proteome analysis of nasal lavage samples after controlled exposure to welding nanoparticles shows an induced acute phase and a nuclear receptor, LXR/RXR, activation that influence the status of the extracellular matrix
title_full Comprehensive proteome analysis of nasal lavage samples after controlled exposure to welding nanoparticles shows an induced acute phase and a nuclear receptor, LXR/RXR, activation that influence the status of the extracellular matrix
title_fullStr Comprehensive proteome analysis of nasal lavage samples after controlled exposure to welding nanoparticles shows an induced acute phase and a nuclear receptor, LXR/RXR, activation that influence the status of the extracellular matrix
title_full_unstemmed Comprehensive proteome analysis of nasal lavage samples after controlled exposure to welding nanoparticles shows an induced acute phase and a nuclear receptor, LXR/RXR, activation that influence the status of the extracellular matrix
title_short Comprehensive proteome analysis of nasal lavage samples after controlled exposure to welding nanoparticles shows an induced acute phase and a nuclear receptor, LXR/RXR, activation that influence the status of the extracellular matrix
title_sort comprehensive proteome analysis of nasal lavage samples after controlled exposure to welding nanoparticles shows an induced acute phase and a nuclear receptor, lxr/rxr, activation that influence the status of the extracellular matrix
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5946400/
https://www.ncbi.nlm.nih.gov/pubmed/29760600
http://dx.doi.org/10.1186/s12014-018-9196-y
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