Ontology highlight
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.
SUBMITTER: Alcorn JF
PROVIDER: S-EPMC2078678 | biostudies-literature | 2007 Nov
REPOSITORIES: biostudies-literature
Alcorn John F JF Rinaldi Lisa M LM Jaffe Elizabeth F EF van Loon Mirjam M Bates Jason H T JH Janssen-Heininger Yvonne M W YM Irvin Charles G CG
American journal of respiratory and critical care medicine 20070829 10
<h4>Rationale</h4>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.<h4>Objectives</h4>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 ...[more]