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.
|Number of pages
|American Journal of Respiratory and Critical Care Medicine
|Published - 15 Mar 2008
- Allergic asthma
- Mouse model