Airway fibroblasts in asthma manifest an invasive phenotype

Am J Respir Crit Care Med. 2011 Jun 15;183(12):1625-32. doi: 10.1164/rccm.201009-1452OC. Epub 2011 Mar 25.


Rationale: Invasive cell phenotypes have been demonstrated in malignant transformation, but not in other diseases, such as asthma. Cellular invasiveness is thought to be mediated by transforming growth factor (TGF)-β1 and matrix metalloproteinases (MMPs). IL-13 is a key T(H)2 cytokine that directs many features of airway remodeling through TGF-β1 and MMPs.

Objectives: We hypothesized that, in human asthma, IL-13 stimulates increased airway fibroblast invasiveness via TGF-β1 and MMPs in asthma compared with normal controls.

Methods: Fibroblasts were cultured from endobronchial biopsies in 20 subjects with mild asthma (FEV(1): 90 ± 3.6% pred) and 17 normal control subjects (FEV(1): 102 ± 2.9% pred) who underwent bronchoscopy. Airway fibroblast invasiveness was investigated using Matrigel chambers. IL-13 or IL-13 with TGF-β1 neutralizing antibody or pan-MMP inhibitor (GM6001) was added to the lower chamber as a chemoattractant. Flow cytometry and immunohistochemistry were performed in a subset of subjects to evaluate IL-13 receptor levels.

Measurements and main results: IL-13 significantly stimulated invasion in asthmatic airway fibroblasts, compared with normal control subjects. Inhibitors of both TGF-β1 and MMPs blocked IL-13-induced invasion in asthma, but had no effect in normal control subjects. At baseline, in airway tissue, IL-13 receptors were expressed in significantly higher levels in asthma, compared with normal control subjects. In airway fibroblasts, baseline IL-13Rα2 was reduced in asthma compared with normal control subjects.

Conclusions: IL-13 potentiates airway fibroblast invasion through a mechanism involving TGF-β1 and MMPs. IL-13 receptor subunits are differentially expressed in asthma. These effects may result in IL-13-directed airway remodeling in asthma.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Airway Remodeling / physiology
  • Asthma / pathology*
  • Bronchi / pathology
  • Cells, Cultured
  • Female
  • Fibroblasts / physiology*
  • Flow Cytometry
  • Humans
  • Immunohistochemistry
  • Interleukin-13 / physiology*
  • Male
  • Matrix Metalloproteinases / physiology
  • Receptors, Interleukin-13 / analysis
  • Transforming Growth Factor beta1 / physiology


  • Interleukin-13
  • Receptors, Interleukin-13
  • Transforming Growth Factor beta1
  • Matrix Metalloproteinases