title: Eosinophils promote epithelial to mesenchymal transition of bronchial epithelial cells.
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.
authors.affiliation: Department of Immunology, Mie University Graduate School of Medicine, Tsu, Mie, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Yasukawa
authors.forename: Koa
authors.initials: K
authors.lastname: Hosoki
authors.forename: Masaaki
authors.initials: M
authors.lastname: Toda
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Miyake
authors.forename: Yuki
authors.initials: Y
authors.lastname: Matsushima
authors.forename: Takahiro
authors.initials: T
authors.lastname: Matsumoto
authors.forename: Daniel
authors.initials: D
authors.lastname: Boveda-Ruiz
authors.forename: Paloma
authors.initials: P
authors.lastname: Gil-Bernabe
authors.forename: Mizuho
authors.initials: M
authors.lastname: Nagao
authors.forename: Mayumi
authors.initials: M
authors.lastname: Sugimoto
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Hiraguchi
authors.forename: Reiko
authors.initials: R
authors.lastname: Tokuda
authors.forename: Masahiro
authors.initials: M
authors.lastname: Naito
authors.forename: Takehiro
authors.initials: T
authors.lastname: Takagi
authors.forename: Corina N
authors.initials: CN
authors.lastname: D'Alessandro-Gabazza
authors.forename: Shigeru
authors.initials: S
authors.lastname: Suga
authors.forename: Tetsu
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Takao
authors.initials: T
authors.lastname: Fujisawa
authors.forename: Osamu
authors.initials: O
authors.lastname: Taguchi
authors.forename: Esteban C
authors.initials: EC
authors.lastname: Gabazza
mesh_terms: D000818:Animals; D001980:Bronchi / Q000378:metabolism* / Q000473:pathology*; D002450:Cell Communication; D002460:Cell Line; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism; D004804:Eosinophils / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology*; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D005355:Fibrosis; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D008168:Lung / Q000378:metabolism / Q000473:pathology; D020935:MAP Kinase Signaling System; D008297:Male; D051379:Mice; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D016207:Cytokines; D053773:Transforming Growth Factor beta1