Simultaneous stimulation with TGF-β1 and TNF-α induces epithelial mesenchymal transition in bronchial epithelial cells

Int Arch Allergy Immunol. 2011;155(2):119-28. doi: 10.1159/000318854. Epub 2010 Dec 22.


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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Airway Remodeling
  • Biomarkers / metabolism
  • Bronchi / cytology*
  • Cadherins / genetics
  • Cadherins / metabolism
  • Cell Line, Transformed
  • Cell Movement / immunology
  • Collagen Type I / genetics
  • Collagen Type I / metabolism
  • Epithelial Cells / cytology
  • Epithelial Cells / immunology
  • Epithelial Cells / metabolism*
  • Epithelial-Mesenchymal Transition / immunology
  • Humans
  • Receptor Cross-Talk* / immunology
  • Transforming Growth Factor beta / immunology
  • Transforming Growth Factor beta / metabolism*
  • Tumor Necrosis Factor-alpha / immunology
  • Tumor Necrosis Factor-alpha / metabolism*
  • Versicans / genetics
  • Versicans / metabolism
  • Vimentin / genetics
  • Vimentin / metabolism


  • Biomarkers
  • Cadherins
  • Collagen Type I
  • Transforming Growth Factor beta
  • Tumor Necrosis Factor-alpha
  • Vimentin
  • Versicans