Cargando…

Thioredoxin-1 Protects against Neutrophilic Inflammation and Emphysema Progression in a Mouse Model of Chronic Obstructive Pulmonary Disease Exacerbation

BACKGROUND: Exacerbations of chronic obstructive pulmonary disease (COPD) are characterized by acute enhancement of airway neutrophilic inflammation under oxidative stress and can be involved in emphysema progression. However, pharmacotherapy against the neutrophilic inflammation and emphysema progr...

Descripción completa

Detalles Bibliográficos
Autores principales: Tanabe, Naoya, Hoshino, Yuma, Marumo, Satoshi, Kiyokawa, Hirofumi, Sato, Susumu, Kinose, Daisuke, Uno, Kazuko, Muro, Shigeo, Hirai, Toyohiro, Yodoi, Junji, Mishima, Michiaki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3823967/
https://www.ncbi.nlm.nih.gov/pubmed/24244404
http://dx.doi.org/10.1371/journal.pone.0079016
_version_ 1782290641726734336
author Tanabe, Naoya
Hoshino, Yuma
Marumo, Satoshi
Kiyokawa, Hirofumi
Sato, Susumu
Kinose, Daisuke
Uno, Kazuko
Muro, Shigeo
Hirai, Toyohiro
Yodoi, Junji
Mishima, Michiaki
author_facet Tanabe, Naoya
Hoshino, Yuma
Marumo, Satoshi
Kiyokawa, Hirofumi
Sato, Susumu
Kinose, Daisuke
Uno, Kazuko
Muro, Shigeo
Hirai, Toyohiro
Yodoi, Junji
Mishima, Michiaki
author_sort Tanabe, Naoya
collection PubMed
description BACKGROUND: Exacerbations of chronic obstructive pulmonary disease (COPD) are characterized by acute enhancement of airway neutrophilic inflammation under oxidative stress and can be involved in emphysema progression. However, pharmacotherapy against the neutrophilic inflammation and emphysema progression associated with exacerbation has not been established. Thioredoxin-1 has anti-oxidative and anti-inflammatory properties and it can ameliorate neutrophilic inflammation through anti-chemotactic effects and prevent cigarette smoke (CS)-induced emphysema. We aimed to determine whether thioredoxin-1 can suppress neutrophilic inflammation and emphysema progression in a mouse model of COPD exacerbation and if so, to reveal the underlying mechanisms. RESULTS: Mice were exposed to CS and then challenged with polyinosine-polycytidylic acid [poly(I:C)], an agonist for virus-induced innate immunity. Airway neutrophilic inflammation, oxidative stress and lung apoptosis were enhanced in smoke-sensitive C57Bl/6, but not in smoke-resistant NZW mice. Exposure to CS and poly(I:C) challenge accelerated emphysema progression in C57Bl/6 mice. Thioredoxin-1 suppressed neutrophilic inflammation and emphysema progression. Poly(I:C) caused early neutrophilic inflammation through keratinocyte-derived chemokine and granulocyte-macrophage colony-stimulating factor (GM-CSF) release in the lung exposed to CS. Late neutrophilic inflammation was caused by persistent GM-CSF release, which thioredoxin-1 ameliorated. Thioredoxin-1 enhanced pulmonary mRNA expression of MAP kinase phosphatase 1 (MKP-1), and the suppressive effects of thioredoxin-1 on prolonged GM-CSF release and late neutrophilic inflammation disappeared by inhibiting MKP-1. CONCLUSION: Using a mouse model of COPD exacerbation, we demonstrated that thioredoxin-1 ameliorated neutrophilic inflammation by suppressing GM-CSF release, which prevented emphysema progression. Our findings deepen understanding of the mechanisms underlying the regulation of neutrophilic inflammation by thioredoxin-1 and indicate that thioredoxin-1 could have potential as a drug to counteract COPD exacerbation.
format Online
Article
Text
id pubmed-3823967
institution National Center for Biotechnology Information
language English
publishDate 2013
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-38239672013-11-15 Thioredoxin-1 Protects against Neutrophilic Inflammation and Emphysema Progression in a Mouse Model of Chronic Obstructive Pulmonary Disease Exacerbation Tanabe, Naoya Hoshino, Yuma Marumo, Satoshi Kiyokawa, Hirofumi Sato, Susumu Kinose, Daisuke Uno, Kazuko Muro, Shigeo Hirai, Toyohiro Yodoi, Junji Mishima, Michiaki PLoS One Research Article BACKGROUND: Exacerbations of chronic obstructive pulmonary disease (COPD) are characterized by acute enhancement of airway neutrophilic inflammation under oxidative stress and can be involved in emphysema progression. However, pharmacotherapy against the neutrophilic inflammation and emphysema progression associated with exacerbation has not been established. Thioredoxin-1 has anti-oxidative and anti-inflammatory properties and it can ameliorate neutrophilic inflammation through anti-chemotactic effects and prevent cigarette smoke (CS)-induced emphysema. We aimed to determine whether thioredoxin-1 can suppress neutrophilic inflammation and emphysema progression in a mouse model of COPD exacerbation and if so, to reveal the underlying mechanisms. RESULTS: Mice were exposed to CS and then challenged with polyinosine-polycytidylic acid [poly(I:C)], an agonist for virus-induced innate immunity. Airway neutrophilic inflammation, oxidative stress and lung apoptosis were enhanced in smoke-sensitive C57Bl/6, but not in smoke-resistant NZW mice. Exposure to CS and poly(I:C) challenge accelerated emphysema progression in C57Bl/6 mice. Thioredoxin-1 suppressed neutrophilic inflammation and emphysema progression. Poly(I:C) caused early neutrophilic inflammation through keratinocyte-derived chemokine and granulocyte-macrophage colony-stimulating factor (GM-CSF) release in the lung exposed to CS. Late neutrophilic inflammation was caused by persistent GM-CSF release, which thioredoxin-1 ameliorated. Thioredoxin-1 enhanced pulmonary mRNA expression of MAP kinase phosphatase 1 (MKP-1), and the suppressive effects of thioredoxin-1 on prolonged GM-CSF release and late neutrophilic inflammation disappeared by inhibiting MKP-1. CONCLUSION: Using a mouse model of COPD exacerbation, we demonstrated that thioredoxin-1 ameliorated neutrophilic inflammation by suppressing GM-CSF release, which prevented emphysema progression. Our findings deepen understanding of the mechanisms underlying the regulation of neutrophilic inflammation by thioredoxin-1 and indicate that thioredoxin-1 could have potential as a drug to counteract COPD exacerbation. Public Library of Science 2013-11-11 /pmc/articles/PMC3823967/ /pubmed/24244404 http://dx.doi.org/10.1371/journal.pone.0079016 Text en © 2013 Tanabe et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Tanabe, Naoya
Hoshino, Yuma
Marumo, Satoshi
Kiyokawa, Hirofumi
Sato, Susumu
Kinose, Daisuke
Uno, Kazuko
Muro, Shigeo
Hirai, Toyohiro
Yodoi, Junji
Mishima, Michiaki
Thioredoxin-1 Protects against Neutrophilic Inflammation and Emphysema Progression in a Mouse Model of Chronic Obstructive Pulmonary Disease Exacerbation
title Thioredoxin-1 Protects against Neutrophilic Inflammation and Emphysema Progression in a Mouse Model of Chronic Obstructive Pulmonary Disease Exacerbation
title_full Thioredoxin-1 Protects against Neutrophilic Inflammation and Emphysema Progression in a Mouse Model of Chronic Obstructive Pulmonary Disease Exacerbation
title_fullStr Thioredoxin-1 Protects against Neutrophilic Inflammation and Emphysema Progression in a Mouse Model of Chronic Obstructive Pulmonary Disease Exacerbation
title_full_unstemmed Thioredoxin-1 Protects against Neutrophilic Inflammation and Emphysema Progression in a Mouse Model of Chronic Obstructive Pulmonary Disease Exacerbation
title_short Thioredoxin-1 Protects against Neutrophilic Inflammation and Emphysema Progression in a Mouse Model of Chronic Obstructive Pulmonary Disease Exacerbation
title_sort thioredoxin-1 protects against neutrophilic inflammation and emphysema progression in a mouse model of chronic obstructive pulmonary disease exacerbation
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3823967/
https://www.ncbi.nlm.nih.gov/pubmed/24244404
http://dx.doi.org/10.1371/journal.pone.0079016
work_keys_str_mv AT tanabenaoya thioredoxin1protectsagainstneutrophilicinflammationandemphysemaprogressioninamousemodelofchronicobstructivepulmonarydiseaseexacerbation
AT hoshinoyuma thioredoxin1protectsagainstneutrophilicinflammationandemphysemaprogressioninamousemodelofchronicobstructivepulmonarydiseaseexacerbation
AT marumosatoshi thioredoxin1protectsagainstneutrophilicinflammationandemphysemaprogressioninamousemodelofchronicobstructivepulmonarydiseaseexacerbation
AT kiyokawahirofumi thioredoxin1protectsagainstneutrophilicinflammationandemphysemaprogressioninamousemodelofchronicobstructivepulmonarydiseaseexacerbation
AT satosusumu thioredoxin1protectsagainstneutrophilicinflammationandemphysemaprogressioninamousemodelofchronicobstructivepulmonarydiseaseexacerbation
AT kinosedaisuke thioredoxin1protectsagainstneutrophilicinflammationandemphysemaprogressioninamousemodelofchronicobstructivepulmonarydiseaseexacerbation
AT unokazuko thioredoxin1protectsagainstneutrophilicinflammationandemphysemaprogressioninamousemodelofchronicobstructivepulmonarydiseaseexacerbation
AT muroshigeo thioredoxin1protectsagainstneutrophilicinflammationandemphysemaprogressioninamousemodelofchronicobstructivepulmonarydiseaseexacerbation
AT hiraitoyohiro thioredoxin1protectsagainstneutrophilicinflammationandemphysemaprogressioninamousemodelofchronicobstructivepulmonarydiseaseexacerbation
AT yodoijunji thioredoxin1protectsagainstneutrophilicinflammationandemphysemaprogressioninamousemodelofchronicobstructivepulmonarydiseaseexacerbation
AT mishimamichiaki thioredoxin1protectsagainstneutrophilicinflammationandemphysemaprogressioninamousemodelofchronicobstructivepulmonarydiseaseexacerbation