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Am J Respir Crit Care Med. 2007 Nov 15;176(10):974-82. Epub 2007 Aug 29.

Transforming growth factor-beta1 suppresses airway hyperresponsiveness in allergic airway disease.

Author information

1
Department of Pathology, University of Vermont, Burlington, Vermont 05405, USA. john.alcorn@med.uvm.edu

Abstract

RATIONALE:

Asthma is characterized by increases in airway resistance, pulmonary remodeling, and lung inflammation. The cytokine transforming growth factor (TGF)-beta has been shown to have a central role in asthma pathogenesis and in mouse models of allergic airway disease.

OBJECTIVES:

To determine the contribution of TGF-beta to airway hyperresponsiveness (AHR), we examined the time course, source, and isoform specificity of TGF-beta production in an in vivo mouse asthma model. To then elucidate the function of TGF-beta in AHR, inflammation, and pulmonary fibrosis, we examined the effects of blocking TGF-beta signaling with neutralizing antibody.

METHODS:

Mice were sensitized and challenged with ovalbumin (OVA) to establish allergic airway disease. TGF-beta activity was neutralized by intranasal administration of monoclonal antibody.

MEASUREMENTS AND MAIN RESULTS:

TGF-beta1 protein levels were increased in OVA-challenged lungs versus naive controls, and airway epithelial cells were shown to be a likely source of TGF-beta1. In addition, TGF-beta1 levels were elevated in OVA-exposed IL-5-null mice, which fail to recruit eosinophils into the airways. Neutralization of TGF-beta1 with specific antibody had no significant effect on airway inflammation and eosinophilia, although anti-TGF-beta1 antibody enhanced OVA-induced AHR and suppressed pulmonary fibrosis.

CONCLUSIONS:

These data show that TGF-beta1 is the main TGF-beta isoform produced after OVA challenge, with a likely cellular source being the airway epithelium. The effects of blocking TGF-beta1 signaling had differential effects on AHR, fibrosis, and inflammation. While TGF-beta neutralization may be beneficial to abrogating airway remodeling, it may be detrimental to lung function by increasing AHR.

PMID:
17761617
PMCID:
PMC2078678
DOI:
10.1164/rccm.200702-334OC
[Indexed for MEDLINE]
Free PMC Article

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