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The Significance of Hypothiocyanite Production via the Pendrin/DUOX/Peroxidase Pathway in the Pathogenesis of Asthma

Inhaled corticosteroids (ICSs) are used as first-line drugs for asthma, and various novel antiasthma drugs targeting type 2 immune mediators are now under development. However, molecularly targeted drugs are expensive, creating an economic burden on patients. We and others previously found pendrin/S...

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Autores principales: Izuhara, Kenji, Suzuki, Shoichi, Ogawa, Masahiro, Nunomura, Satoshi, Nanri, Yasuhiro, Mitamura, Yasutaka, Yoshihara, Tomohito
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5735670/
https://www.ncbi.nlm.nih.gov/pubmed/29359006
http://dx.doi.org/10.1155/2017/1054801
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author Izuhara, Kenji
Suzuki, Shoichi
Ogawa, Masahiro
Nunomura, Satoshi
Nanri, Yasuhiro
Mitamura, Yasutaka
Yoshihara, Tomohito
author_facet Izuhara, Kenji
Suzuki, Shoichi
Ogawa, Masahiro
Nunomura, Satoshi
Nanri, Yasuhiro
Mitamura, Yasutaka
Yoshihara, Tomohito
author_sort Izuhara, Kenji
collection PubMed
description Inhaled corticosteroids (ICSs) are used as first-line drugs for asthma, and various novel antiasthma drugs targeting type 2 immune mediators are now under development. However, molecularly targeted drugs are expensive, creating an economic burden on patients. We and others previously found pendrin/SLC26A4 as a downstream molecule of IL-13, a signature type 2 cytokine critical for asthma, and showed its significance in the pathogenesis of asthma using model mice. However, the molecular mechanism of how pendrin causes airway inflammation remained elusive. We have recently demonstrated that hypothiocyanite (OSCN(−)) produced by the pendrin/DUOX/peroxidase pathway has the potential to cause airway inflammation. Pendrin transports thiocyanate (SCN(−)) into pulmonary lumens at the apical side. Peroxidases catalyze SCN(−) and H(2)O(2) generated by DUOX into OSCN(−). Low doses of OSCN(−) activate NF-κB in airway epithelial cells, whereas OSCN(−) in high doses causes necrosis of the cells, inducing the release of IL-33 and accelerating inflammation. OSCN(−) production is augmented in asthma model mice and possibly in some asthma patients. Heme peroxidase inhibitors, widely used as antithyroid agents, diminish asthma-like phenotypes in mice, indicating the significance of this pathway. These findings suggest the possibility of repositioning antithyroid agents as antiasthma drugs.
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spelling pubmed-57356702018-01-22 The Significance of Hypothiocyanite Production via the Pendrin/DUOX/Peroxidase Pathway in the Pathogenesis of Asthma Izuhara, Kenji Suzuki, Shoichi Ogawa, Masahiro Nunomura, Satoshi Nanri, Yasuhiro Mitamura, Yasutaka Yoshihara, Tomohito Oxid Med Cell Longev Review Article Inhaled corticosteroids (ICSs) are used as first-line drugs for asthma, and various novel antiasthma drugs targeting type 2 immune mediators are now under development. However, molecularly targeted drugs are expensive, creating an economic burden on patients. We and others previously found pendrin/SLC26A4 as a downstream molecule of IL-13, a signature type 2 cytokine critical for asthma, and showed its significance in the pathogenesis of asthma using model mice. However, the molecular mechanism of how pendrin causes airway inflammation remained elusive. We have recently demonstrated that hypothiocyanite (OSCN(−)) produced by the pendrin/DUOX/peroxidase pathway has the potential to cause airway inflammation. Pendrin transports thiocyanate (SCN(−)) into pulmonary lumens at the apical side. Peroxidases catalyze SCN(−) and H(2)O(2) generated by DUOX into OSCN(−). Low doses of OSCN(−) activate NF-κB in airway epithelial cells, whereas OSCN(−) in high doses causes necrosis of the cells, inducing the release of IL-33 and accelerating inflammation. OSCN(−) production is augmented in asthma model mice and possibly in some asthma patients. Heme peroxidase inhibitors, widely used as antithyroid agents, diminish asthma-like phenotypes in mice, indicating the significance of this pathway. These findings suggest the possibility of repositioning antithyroid agents as antiasthma drugs. Hindawi 2017 2017-11-22 /pmc/articles/PMC5735670/ /pubmed/29359006 http://dx.doi.org/10.1155/2017/1054801 Text en Copyright © 2017 Kenji Izuhara et al. http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Review Article
Izuhara, Kenji
Suzuki, Shoichi
Ogawa, Masahiro
Nunomura, Satoshi
Nanri, Yasuhiro
Mitamura, Yasutaka
Yoshihara, Tomohito
The Significance of Hypothiocyanite Production via the Pendrin/DUOX/Peroxidase Pathway in the Pathogenesis of Asthma
title The Significance of Hypothiocyanite Production via the Pendrin/DUOX/Peroxidase Pathway in the Pathogenesis of Asthma
title_full The Significance of Hypothiocyanite Production via the Pendrin/DUOX/Peroxidase Pathway in the Pathogenesis of Asthma
title_fullStr The Significance of Hypothiocyanite Production via the Pendrin/DUOX/Peroxidase Pathway in the Pathogenesis of Asthma
title_full_unstemmed The Significance of Hypothiocyanite Production via the Pendrin/DUOX/Peroxidase Pathway in the Pathogenesis of Asthma
title_short The Significance of Hypothiocyanite Production via the Pendrin/DUOX/Peroxidase Pathway in the Pathogenesis of Asthma
title_sort significance of hypothiocyanite production via the pendrin/duox/peroxidase pathway in the pathogenesis of asthma
topic Review Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5735670/
https://www.ncbi.nlm.nih.gov/pubmed/29359006
http://dx.doi.org/10.1155/2017/1054801
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