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

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

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  • 1Department of Pathology and Molecular Medicine, Head, Division of Respiratory Diseases and Allergy, MDCL 4013, McMaster University, 1200 Main Street West, Hamilton, ON, Canada. jordanam@mcmaster.ca

Abstract

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.

PMID:
18174546
[PubMed - indexed for MEDLINE]
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