title: Simultaneous stimulation with TGF-β1 and TNF-α induces epithelial mesenchymal transition in bronchial epithelial cells.
abstract: BACKGROUND
  Airway remodeling is an important feature of chronic airway disease, but the mechanisms involved remain unclear. Recently, epithelial mesenchymal transition (EMT) was reported to be associated with tissue fibrosis. TGF-β1, which is a potent inducer of EMT, is thought to be related to the pathogenesis of airway remodeling. We investigated whether TGF-β1 and/or TNF-α induce EMT in bronchial epithelial cells.
  
  
  METHODS
  Cultured BEAS-2B cells and primary normal human bronchial epithelial cells (NHBE) were treated with TGF-β1 and/or TNF-α. Morphological changes and the expression of EMT-related markers were evaluated by immunocytochemical staining. Expressions of EMT-related markers, extracellular matrix (ECM) components (collagen type I and versican), and TGF-β receptors I, II, and III were analyzed by quantitative RT-PCR. Migration was evaluated using the Boyden chamber technique.
  
  
  RESULTS
  The TGF-β1-induced EMT in BEAS-2B cells was demonstrated on the basis of morphological changes and the downregulation of E-cadherin. Costimulation with TNF-α enhanced the TGF-β1-induced morphological changes and increased vimentin expression. Treatment with TGF-β1 increased the expression of collagen type I and versican. EMT induced with TGF-β1 plus TNF-α promoted cell migration. Stimulation of NHBE with TGF-β1 led to EMT.
  
  
  CONCLUSIONS
  TGF-β1 induced EMT in BEAS-2B cells, and costimulation with TNF-α enhanced the EMT. As a result of the EMT process, BEAS-2B cells acquired functions of mesenchymal cells. In addition, TGF-β1 treatment induced EMT in NHBE as shown by changes in EMT-related markers. Bronchial epithelial cells might contribute to airway remodeling through EMT.
authors.affiliation: Department of Respiratory Medicine, University of Tokyo Graduate School of Medicine, Tokyo, Japan. sumihzt01@yahoo.co.jp
authors.forename: Sumiko
authors.initials: S
authors.lastname: Kamitani
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Yamauchi
authors.forename: Shin
authors.initials: S
authors.lastname: Kawasaki
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Takami
authors.forename: Hajime
authors.initials: H
authors.lastname: Takizawa
authors.forename: Takahide
authors.initials: T
authors.lastname: Nagase
authors.forename: Tadashi
authors.initials: T
authors.lastname: Kohyama
mesh_terms: D056151:Airway Remodeling; D015415:Biomarkers / Q000378:metabolism; D001980:Bronchi / Q000166:cytology*; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002461:Cell Line, Transformed; D002465:Cell Movement / Q000276:immunology; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D058750:Epithelial-Mesenchymal Transition / Q000276:immunology; D006801:Humans; D020239:Receptor Cross-Talk / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000276:immunology / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism*; D053675:Versicans / Q000235:genetics / Q000378:metabolism; D014746:Vimentin / Q000235:genetics / Q000378:metabolism
chemical_list: D015415:Biomarkers; D015820:Cadherins; D024042:Collagen Type I; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D014746:Vimentin; D053675:Versicans