Transforming growth factor-β regulates house dust mite–induced allergic airway inflammation but not airway remodeling
R Fattouh, NG Midence, K Arias… - American journal of …, 2008 - atsjournals.org
R Fattouh, NG Midence, K Arias, JR Johnson, TD Walker, S Goncharova, KP Souza…
American journal of respiratory and critical care medicine, 2008•atsjournals.orgRationale: 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 …
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 …
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.
ATS Journals