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Linoleic acid metabolite drives severe asthma by causing airway epithelial injury
Airway epithelial injury is the hallmark of various respiratory diseases, but its mechanisms remain poorly understood. While 13-S-hydroxyoctadecadienoic acid (13-S-HODE) is produced in high concentration during mitochondrial degradation in reticulocytes little is known about its role in asthma patho...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3583002/ https://www.ncbi.nlm.nih.gov/pubmed/23443229 http://dx.doi.org/10.1038/srep01349 |
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author | Mabalirajan, Ulaganathan Rehman, Rakhshinda Ahmad, Tanveer Kumar, Sarvesh Singh, Suchita Leishangthem, Geeta D. Aich, Jyotirmoi Kumar, Manish Khanna, Kritika Singh, Vijay P. Dinda, Amit K. Biswal, Shyam Agrawal, Anurag Ghosh, Balaram |
author_facet | Mabalirajan, Ulaganathan Rehman, Rakhshinda Ahmad, Tanveer Kumar, Sarvesh Singh, Suchita Leishangthem, Geeta D. Aich, Jyotirmoi Kumar, Manish Khanna, Kritika Singh, Vijay P. Dinda, Amit K. Biswal, Shyam Agrawal, Anurag Ghosh, Balaram |
author_sort | Mabalirajan, Ulaganathan |
collection | PubMed |
description | Airway epithelial injury is the hallmark of various respiratory diseases, but its mechanisms remain poorly understood. While 13-S-hydroxyoctadecadienoic acid (13-S-HODE) is produced in high concentration during mitochondrial degradation in reticulocytes little is known about its role in asthma pathogenesis. Here, we show that extracellular 13-S-HODE induces mitochondrial dysfunction and airway epithelial apoptosis. This is associated with features of severe airway obstruction, lung remodeling, increase in epithelial stress related proinflammatory cytokines and drastic airway neutrophilia in mouse. Further, 13-S-HODE induced features are attenuated by inhibiting Transient Receptor Potential Cation Channel, Vanilloid-type 1 (TRPV1) both in mouse model and human bronchial epithelial cells. These findings are relevant to human asthma, as 13-S-HODE levels are increased in human asthmatic airways. Blocking of 13-S-HODE activity or disruption of TRPV1 activity attenuated airway injury and asthma mimicking features in murine allergic airway inflammation. These findings indicate that 13-S-HODE induces mitochondrial dysfunction and airway epithelial injury. |
format | Online Article Text |
id | pubmed-3583002 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-35830022013-02-27 Linoleic acid metabolite drives severe asthma by causing airway epithelial injury Mabalirajan, Ulaganathan Rehman, Rakhshinda Ahmad, Tanveer Kumar, Sarvesh Singh, Suchita Leishangthem, Geeta D. Aich, Jyotirmoi Kumar, Manish Khanna, Kritika Singh, Vijay P. Dinda, Amit K. Biswal, Shyam Agrawal, Anurag Ghosh, Balaram Sci Rep Article Airway epithelial injury is the hallmark of various respiratory diseases, but its mechanisms remain poorly understood. While 13-S-hydroxyoctadecadienoic acid (13-S-HODE) is produced in high concentration during mitochondrial degradation in reticulocytes little is known about its role in asthma pathogenesis. Here, we show that extracellular 13-S-HODE induces mitochondrial dysfunction and airway epithelial apoptosis. This is associated with features of severe airway obstruction, lung remodeling, increase in epithelial stress related proinflammatory cytokines and drastic airway neutrophilia in mouse. Further, 13-S-HODE induced features are attenuated by inhibiting Transient Receptor Potential Cation Channel, Vanilloid-type 1 (TRPV1) both in mouse model and human bronchial epithelial cells. These findings are relevant to human asthma, as 13-S-HODE levels are increased in human asthmatic airways. Blocking of 13-S-HODE activity or disruption of TRPV1 activity attenuated airway injury and asthma mimicking features in murine allergic airway inflammation. These findings indicate that 13-S-HODE induces mitochondrial dysfunction and airway epithelial injury. Nature Publishing Group 2013-02-27 /pmc/articles/PMC3583002/ /pubmed/23443229 http://dx.doi.org/10.1038/srep01349 Text en Copyright © 2013, Macmillan Publishers Limited. All rights reserved http://creativecommons.org/licenses/by-nc-nd/3.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/ |
spellingShingle | Article Mabalirajan, Ulaganathan Rehman, Rakhshinda Ahmad, Tanveer Kumar, Sarvesh Singh, Suchita Leishangthem, Geeta D. Aich, Jyotirmoi Kumar, Manish Khanna, Kritika Singh, Vijay P. Dinda, Amit K. Biswal, Shyam Agrawal, Anurag Ghosh, Balaram Linoleic acid metabolite drives severe asthma by causing airway epithelial injury |
title | Linoleic acid metabolite drives severe asthma by causing airway epithelial injury |
title_full | Linoleic acid metabolite drives severe asthma by causing airway epithelial injury |
title_fullStr | Linoleic acid metabolite drives severe asthma by causing airway epithelial injury |
title_full_unstemmed | Linoleic acid metabolite drives severe asthma by causing airway epithelial injury |
title_short | Linoleic acid metabolite drives severe asthma by causing airway epithelial injury |
title_sort | linoleic acid metabolite drives severe asthma by causing airway epithelial injury |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3583002/ https://www.ncbi.nlm.nih.gov/pubmed/23443229 http://dx.doi.org/10.1038/srep01349 |
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