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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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) |
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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 |
work_keys_str_mv |
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