Interleukin-13 induces proliferation of human airway epithelial cells in vitro via a mechanism mediated by transforming growth factor-alpha

Am J Respir Cell Mol Biol. 2001 Dec;25(6):739-43. doi: 10.1165/ajrcmb.25.6.4659.


Remodeling of the airways, as occurs in asthmatic patients, is associated with the continual presence of inflammatory mediators and Th2 cytokines, especially interleukin (IL)-13, during cycles of epithelial injury and repair. In this study, we examined the effect of IL-13 on well-differentiated normal human bronchial epithelial (NHBE) cells maintained in air-liquid interface culture. IL-13 induced proliferation of NHBE cells after 24 h exposure, as reflected by [(3)H]thymidine uptake and cell counts. The effects of IL-13 were mediated through the epidermal growth factor receptor (EGFR), as proliferation was attenuated by AG1478, an EGFR tyrosine kinase inhibitor. Proliferation appeared to be mediated by transforming growth factor (TGF)-alpha, a potent ligand for EGFR, which was released rapidly from NHBE cells in response to IL-13. Neutralizing antibody to TGF-alpha, but not antibodies against other potentially important growth factors (EGF, heparin binding epidermal growth factor-like growth factor [HB-EGF], platelet-derived growth factor [PDGF]), inhibited the mitogenic response to IL-13. This study provides the first experimental evidence that IL-13 can initiate a proliferative response of human airway epithelium in the absence of inflammatory cells or other cell types. The results are consistent with a mechanism whereby IL-13 induces release of TGF-alpha from the epithelial cells, which in turn binds via an autocrine/paracrine-type action to the EGFR, initiating proliferation. IL-13-induced airway remodeling in vivo may involve this epithelium-driven response.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Bronchi / cytology
  • Bronchi / drug effects*
  • Cell Division / drug effects
  • Cells, Cultured / cytology
  • Cells, Cultured / drug effects
  • Enzyme Inhibitors / pharmacology
  • Epithelial Cells / cytology
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism
  • ErbB Receptors / antagonists & inhibitors
  • ErbB Receptors / physiology*
  • Humans
  • Interleukin-13 / pharmacology*
  • Models, Biological
  • Quinazolines
  • Signal Transduction / drug effects*
  • Signal Transduction / physiology
  • Transforming Growth Factor alpha / antagonists & inhibitors
  • Transforming Growth Factor alpha / immunology
  • Transforming Growth Factor alpha / metabolism*
  • Tyrphostins / pharmacology


  • Enzyme Inhibitors
  • Interleukin-13
  • Quinazolines
  • Transforming Growth Factor alpha
  • Tyrphostins
  • RTKI cpd
  • ErbB Receptors