RRC ID 44452
Author Yasukawa A, Hosoki K, Toda M, Miyake Y, Matsushima Y, Matsumoto T, Boveda-Ruiz D, Gil-Bernabe P, Nagao M, Sugimoto M, Hiraguchi Y, Tokuda R, Naito M, Takagi T, D'Alessandro-Gabazza CN, Suga S, Kobayashi T, Fujisawa T, Taguchi O, Gabazza EC.
Title Eosinophils promote epithelial to mesenchymal transition of bronchial epithelial cells.
Journal PLoS One
Abstract 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.
Volume 8(5)
Pages e64281
Published 2013-1-1
DOI 10.1371/journal.pone.0064281
PII PONE-D-12-35058
PMID 23700468
PMC PMC3660301
MeSH Animals Bronchi / metabolism* Bronchi / pathology* Cell Communication Cell Line Coculture Techniques Cytokines / metabolism Eosinophils / metabolism* Epithelial Cells / metabolism* Epithelial Cells / pathology* Epithelial-Mesenchymal Transition* Female Fibrosis Humans Inflammation / metabolism Inflammation / pathology Lung / metabolism Lung / pathology MAP Kinase Signaling System Male Mice Transforming Growth Factor beta1 / metabolism
IF 2.74
Times Cited 33
WOS Category RESPIRATORY SYSTEM
Resource
Human and Animal Cells EoL-1 cell(RCB0641)