Transforming growth factor-beta regulates house dust mite-induced allergic airway inflammation but not airway remodeling

Am J Respir Crit Care Med. 2008 Mar 15;177(6):593-603. doi: 10.1164/rccm.200706-958OC. Epub 2008 Jan 3.


Rationale: It is now believed that both chronic airway inflammation and remodeling contribute significantly to airway dysfunction and clinical symptoms in allergic asthma. Transforming growth factor (TGF)-beta is a powerful regulator of both the tissue repair and inflammatory responses, and numerous experimental and clinical studies suggest that it may play an integral role in the pathogenesis of asthma.

Objectives: We investigated the role of TGF-beta in the regulation of allergic airway inflammation and remodeling using a mouse model of house dust mite (HDM)-induced chronic allergic airway disease.

Methods: We have previously shown that intranasal administration of an HDM extract (5 d/wk for 5 wk) elicits robust Th2-polarized airway inflammation and remodeling that is associated with increased airway hyperreactivity. Here, Balb/c mice were similarly exposed to HDM and concurrently treated with a pan-specific TGF-beta neutralizing antibody.

Measurements and main results: We observed that anti-TGF-beta treatment in the context of either continuous or intermittent HDM exposure had no effect on the development of HDM-induced airway remodeling. To further confirm these findings, we also subjected SMAD3 knockout mice to 5 weeks of HDM and observed that knockout mice developed airway remodeling to the same extent as HDM-exposed littermate controls. Notably, TGF-beta neutralization exacerbated the eosinophilic infiltrate and led to increased airway hyperreactivity.

Conclusions: Collectively, these data suggest that TGF-beta regulates HDM-induced chronic airway inflammation but not remodeling, and furthermore, caution against the use of therapeutic strategies aimed at interfering with TGF-beta activity in the treatment of this disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Asthma / immunology
  • Asthma / physiopathology*
  • Bronchial Hyperreactivity / immunology
  • Bronchial Hyperreactivity / physiopathology*
  • Bronchial Provocation Tests
  • Eosinophils
  • Female
  • Hypersensitivity / immunology*
  • Lung / immunology
  • Lung / pathology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Pyroglyphidae / immunology*
  • Smad3 Protein / genetics
  • Smad3 Protein / immunology
  • Transforming Growth Factor beta / physiology*


  • Smad3 Protein
  • Smad3 protein, mouse
  • Transforming Growth Factor beta