title: Transforming growth factor-beta regulates house dust mite-induced allergic airway inflammation but not airway remodeling.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Department 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
authors.forename: Ramzi
authors.initials: R
authors.lastname: Fattouh
authors.forename: N Gabriela
authors.initials: NG
authors.lastname: Midence
authors.forename: Katherine
authors.initials: K
authors.lastname: Arias
authors.forename: Jill R
authors.initials: JR
authors.lastname: Johnson
authors.forename: Tina D
authors.initials: TD
authors.lastname: Walker
authors.forename: Susanna
authors.initials: S
authors.lastname: Goncharova
authors.forename: Kailene P
authors.initials: KP
authors.lastname: Souza
authors.forename: Richard C
authors.initials: RC
authors.lastname: Gregory
authors.forename: Scott
authors.initials: S
authors.lastname: Lonning
authors.forename: Jack
authors.initials: J
authors.lastname: Gauldie
authors.forename: Manel
authors.initials: M
authors.lastname: Jordana
mesh_terms: D000818:Animals; D001249:Asthma / Q000276:immunology / Q000503:physiopathology*; D016535:Bronchial Hyperreactivity / Q000276:immunology / Q000503:physiopathology*; D001985:Bronchial Provocation Tests; D004804:Eosinophils; D005260:Female; D006967:Hypersensitivity / Q000276:immunology*; D008168:Lung / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D039981:Pyroglyphidae / Q000276:immunology*; D051900:Smad3 Protein / Q000235:genetics / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000502:physiology*
chemical_list: D051900:Smad3 Protein; C497791:Smad3 protein, mouse; D016212:Transforming Growth Factor beta