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

Am J Respir Crit Care Med. 2007 Nov 15;176(10):974-82. doi: 10.1164/rccm.200702-334OC. Epub 2007 Aug 29.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antibodies, Monoclonal / pharmacology
  • Asthma / etiology
  • Asthma / pathology*
  • Asthma / physiopathology*
  • Bronchial Hyperreactivity / etiology
  • Bronchial Hyperreactivity / physiopathology*
  • Bronchial Hyperreactivity / prevention & control
  • Disease Models, Animal
  • Female
  • Immunologic Factors / pharmacology
  • Lung / physiopathology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Ovalbumin
  • Transforming Growth Factor beta1 / antagonists & inhibitors
  • Transforming Growth Factor beta1 / physiology*


  • Antibodies, Monoclonal
  • Immunologic Factors
  • Transforming Growth Factor beta1
  • Ovalbumin