title: Transforming growth factor-beta1 suppresses airway hyperresponsiveness in allergic airway disease.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Department of Pathology, University of Vermont, Burlington, Vermont 05405, USA. john.alcorn@med.uvm.edu
authors.forename: John F
authors.initials: JF
authors.lastname: Alcorn
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Rinaldi
authors.forename: Elizabeth F
authors.initials: EF
authors.lastname: Jaffe
authors.forename: Mirjam
authors.initials: M
authors.lastname: van Loon
authors.forename: Jason H T
authors.initials: JH
authors.lastname: Bates
authors.forename: Yvonne M W
authors.initials: YM
authors.lastname: Janssen-Heininger
authors.forename: Charles G
authors.initials: CG
authors.lastname: Irvin
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001249:Asthma / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology*; D016535:Bronchial Hyperreactivity / Q000209:etiology / Q000503:physiopathology* / Q000517:prevention & control; D004195:Disease Models, Animal; D005260:Female; D007155:Immunologic Factors / Q000494:pharmacology; D008168:Lung / Q000503:physiopathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010047:Ovalbumin; D053773:Transforming Growth Factor beta1 / Q000037:antagonists & inhibitors / Q000502:physiology*
chemical_list: D000911:Antibodies, Monoclonal; D007155:Immunologic Factors; D053773:Transforming Growth Factor beta1; D010047:Ovalbumin