Eosinophils promote epithelial to mesenchymal transition of bronchial epithelial cells.

Eosinophilic inflammation and remodeling of the airways including subepithelial fibrosis and myofibroblast hyperplasia are characteristic pathological findings of bronchial asthma. Epithelial to mesenchymal transition (EMT) plays a critical role in airway remodelling. In this study, we hypothesized...

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Autores principales: Atsushi Yasukawa, Koa Hosoki, Masaaki Toda, Yasushi Miyake, Yuki Matsushima, Takahiro Matsumoto, Daniel Boveda-Ruiz, Paloma Gil-Bernabe, Mizuho Nagao, Mayumi Sugimoto, Yukiko Hiraguchi, Reiko Tokuda, Masahiro Naito, Takehiro Takagi, Corina N D'Alessandro-Gabazza, Shigeru Suga, Tetsu Kobayashi, Takao Fujisawa, Osamu Taguchi, Esteban C Gabazza
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Publicado: Public Library of Science (PLoS) 2013
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spelling oai:doaj.org-article:624fd18eef824ff3a3d570e05a9422212021-11-18T07:45:05ZEosinophils promote epithelial to mesenchymal transition of bronchial epithelial cells.1932-620310.1371/journal.pone.0064281https://doaj.org/article/624fd18eef824ff3a3d570e05a9422212013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23700468/?tool=EBIhttps://doaj.org/toc/1932-6203Eosinophilic inflammation and remodeling of the airways including subepithelial fibrosis and myofibroblast hyperplasia are characteristic pathological findings of bronchial asthma. Epithelial to mesenchymal transition (EMT) plays a critical role in airway remodelling. In this study, we hypothesized that infiltrating eosinophils promote airway remodelling in bronchial asthma. To demonstrate this hypothesis we evaluated the effect of eosinophils on EMT by in vitro and in vivo studies. EMT was assessed in mice that received intra-tracheal instillation of mouse bone marrow derived eosinophils and in human bronchial epithelial cells co-cultured with eosinophils freshly purified from healthy individuals or with eosinophilic leukemia cell lines. Intra-tracheal instillation of eosinophils was associated with enhanced bronchial inflammation and fibrosis and increased lung concentration of growth factors. Mice instilled with eosinophils pre-treated with transforming growth factor(TGF)-β1 siRNA had decreased bronchial wall fibrosis compared to controls. EMT was induced in bronchial epithelial cells co-cultured with human eosinophils and it was associated with increased expression of TGF-β1 and Smad3 phosphorylation in the bronchial epithelial cells. Treatment with anti-TGF-β1 antibody blocked EMT in bronchial epithelial cells. Eosinophils induced EMT in bronchial epithelial cells, suggesting their contribution to the pathogenesis of airway remodelling.Atsushi YasukawaKoa HosokiMasaaki TodaYasushi MiyakeYuki MatsushimaTakahiro MatsumotoDaniel Boveda-RuizPaloma Gil-BernabeMizuho NagaoMayumi SugimotoYukiko HiraguchiReiko TokudaMasahiro NaitoTakehiro TakagiCorina N D'Alessandro-GabazzaShigeru SugaTetsu KobayashiTakao FujisawaOsamu TaguchiEsteban C GabazzaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 5, p e64281 (2013)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Atsushi Yasukawa
Koa Hosoki
Masaaki Toda
Yasushi Miyake
Yuki Matsushima
Takahiro Matsumoto
Daniel Boveda-Ruiz
Paloma Gil-Bernabe
Mizuho Nagao
Mayumi Sugimoto
Yukiko Hiraguchi
Reiko Tokuda
Masahiro Naito
Takehiro Takagi
Corina N D'Alessandro-Gabazza
Shigeru Suga
Tetsu Kobayashi
Takao Fujisawa
Osamu Taguchi
Esteban C Gabazza
Eosinophils promote epithelial to mesenchymal transition of bronchial epithelial cells.
description Eosinophilic inflammation and remodeling of the airways including subepithelial fibrosis and myofibroblast hyperplasia are characteristic pathological findings of bronchial asthma. Epithelial to mesenchymal transition (EMT) plays a critical role in airway remodelling. In this study, we hypothesized that infiltrating eosinophils promote airway remodelling in bronchial asthma. To demonstrate this hypothesis we evaluated the effect of eosinophils on EMT by in vitro and in vivo studies. EMT was assessed in mice that received intra-tracheal instillation of mouse bone marrow derived eosinophils and in human bronchial epithelial cells co-cultured with eosinophils freshly purified from healthy individuals or with eosinophilic leukemia cell lines. Intra-tracheal instillation of eosinophils was associated with enhanced bronchial inflammation and fibrosis and increased lung concentration of growth factors. Mice instilled with eosinophils pre-treated with transforming growth factor(TGF)-β1 siRNA had decreased bronchial wall fibrosis compared to controls. EMT was induced in bronchial epithelial cells co-cultured with human eosinophils and it was associated with increased expression of TGF-β1 and Smad3 phosphorylation in the bronchial epithelial cells. Treatment with anti-TGF-β1 antibody blocked EMT in bronchial epithelial cells. Eosinophils induced EMT in bronchial epithelial cells, suggesting their contribution to the pathogenesis of airway remodelling.
format article
author Atsushi Yasukawa
Koa Hosoki
Masaaki Toda
Yasushi Miyake
Yuki Matsushima
Takahiro Matsumoto
Daniel Boveda-Ruiz
Paloma Gil-Bernabe
Mizuho Nagao
Mayumi Sugimoto
Yukiko Hiraguchi
Reiko Tokuda
Masahiro Naito
Takehiro Takagi
Corina N D'Alessandro-Gabazza
Shigeru Suga
Tetsu Kobayashi
Takao Fujisawa
Osamu Taguchi
Esteban C Gabazza
author_facet Atsushi Yasukawa
Koa Hosoki
Masaaki Toda
Yasushi Miyake
Yuki Matsushima
Takahiro Matsumoto
Daniel Boveda-Ruiz
Paloma Gil-Bernabe
Mizuho Nagao
Mayumi Sugimoto
Yukiko Hiraguchi
Reiko Tokuda
Masahiro Naito
Takehiro Takagi
Corina N D'Alessandro-Gabazza
Shigeru Suga
Tetsu Kobayashi
Takao Fujisawa
Osamu Taguchi
Esteban C Gabazza
author_sort Atsushi Yasukawa
title Eosinophils promote epithelial to mesenchymal transition of bronchial epithelial cells.
title_short Eosinophils promote epithelial to mesenchymal transition of bronchial epithelial cells.
title_full Eosinophils promote epithelial to mesenchymal transition of bronchial epithelial cells.
title_fullStr Eosinophils promote epithelial to mesenchymal transition of bronchial epithelial cells.
title_full_unstemmed Eosinophils promote epithelial to mesenchymal transition of bronchial epithelial cells.
title_sort eosinophils promote epithelial to mesenchymal transition of bronchial epithelial cells.
publisher Public Library of Science (PLoS)
publishDate 2013
url https://doaj.org/article/624fd18eef824ff3a3d570e05a942221
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