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

Ramzi Fattouh, N. Gabriela Midence, Katherine Arias, Jill R. Johnson, Tina D. Walker, Susanna Goncharova, Kailene P. Souza, Richard C. Gregory, Scott Lonning, Jack Gauldie, Manel Jordana*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


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)-β 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-β 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-β neutralizing antibody. Measurements and Main Results: We observed that anti-TGF-β 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-β neutralization exacerbated the eosinophilic infiltrate and led to increased airway hyperreactivity. Conclusions: Collectively, these data suggest that TGF-β regulates HDM-induced chronic airway inflammation but not remodeling, and furthermore, caution against the use of therapeutic strategies aimed at interfering with TGF-β activity in the treatment of this disease.

Original languageEnglish
Pages (from-to)593-603
Number of pages11
JournalAmerican Journal of Respiratory and Critical Care Medicine
Issue number6
Publication statusPublished - 15 Mar 2008


  • Allergic asthma
  • Immunology
  • Lung
  • Mouse model


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