Inflammation and epithelial to mesenchymal transition in lung transplant recipients: role in dysregulated epithelial wound repair

Am J Transplant. 2010 Mar;10(3):498-509. doi: 10.1111/j.1600-6143.2009.02953.x. Epub 2010 Jan 5.


Epithelial to mesenchymal transition (EMT) has been implicated in the pathogenesis of obliterative bronchiolitis (OB) after lung transplant. Although TNF-alpha accentuates TGF-beta1 driven EMT in primary human bronchial epithelial cells (PBECs), we hypothesized that other acute pro-inflammatory cytokines elevated in the airways of patients with OB may also accentuate EMT and contribute to dysregulated epithelial wound repair. PBECs from lung transplant recipients were stimulated with TGF-beta1+/-IL-1beta, IL-8, TNF-alpha or activated macrophages in co-culture and EMT assessed. The quality and rate of wound closure in a standardized model of lung epithelial injury was assessed in response to above stimuli. Co-treatment with TGF-beta1+TNF-alpha or IL-1beta significantly accentuates phenotypic and some functional features of EMT compared to TGF-beta1 alone. Co-treatment with TGF-beta1+TNF-alpha or IL-1beta accelerates epithelial wound closure however the quality of repair is highly dysregulated. Co-treatment with TGF-beta1+IL-8 has no significant effect on EMT or the speed or quality of wound healing. Activated macrophages dramatically accentuate TGF-beta1-driven EMT and cause dysregulated wound repair. Crosstalk between macrophage-derived acute inflammation in the airway and elevated TGF-beta1 may favor dysregulated airway epithelial repair and fibrosis in the lung allograft via EMT.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Coculture Techniques
  • Epithelium / pathology*
  • Fibrosis / pathology
  • Humans
  • Inflammation*
  • Interleukin-1beta / metabolism
  • Interleukin-8 / metabolism
  • Lung Transplantation / methods*
  • Macrophages / metabolism
  • Mesoderm / cytology*
  • Models, Biological
  • Transforming Growth Factor beta1 / metabolism
  • Tumor Necrosis Factor-alpha / metabolism
  • Wound Healing*


  • Interleukin-1beta
  • Interleukin-8
  • Transforming Growth Factor beta1
  • Tumor Necrosis Factor-alpha