title: Follistatin is a candidate endogenous negative regulator of activin A in experimental allergic asthma.
abstract: BACKGROUND
  Activin A is a member of the transforming growth factor-beta superfamily which is directly implicated in airway structural change and inflammation in asthma. In vitro, the biological effects of activin A are neutralized by the soluble binding protein follistatin.
  
  
  OBJECTIVE
  To determine the potential of endogenous follistatin to suppress activin A in vivo by analysing their relative tissue and kinetic compartmentalization during the effector phase of subchronic Th2-driven mucosal inflammation in a murine model of allergic asthma.
  
  
  METHODS
  Eosinophilic mucosal inflammation was elicited by triggering Th2 recall responses by antigen challenge in ovalbumin-sensitized BALB/c mice. The kinetics and distribution of activin A and follistatin protein were assessed in lung tissue and bronchoalveolar lavage fluid and measured in relation to airway eosinophilia, goblet cell metaplasia and Th2 cytokine production in mediastinal lymph nodes.
  
  
  RESULTS
  Follistatin was released concurrently with activin A suggesting it acts as an endogenous regulator: peak BAL concentrations coincided with maximal airway eosinophilia, and frequency of IL-4, IL-5 and IL-13 producing cells in mediastinal lymph nodes but induction lagged behind the onset of inflammation. Follistatin and activin A immunoreactivity were lost in airway epithelial cells in parallel with goblet cell metaplasia. Exogenous follistatin inhibited the allergen-specific Th2 immune response in mediastinal lymph nodes and mucus production in the lung.
  
  
  CONCLUSIONS
  Follistatin is preformed in the normal lung and released in concert with activin A suggesting it serves as an endogenous regulator. Disturbance of the fine balance between activin A and its endogenous inhibitor follistatin may be a determinant of the severity of allergic inflammation or tissue phenotypic shift in asthma.
authors.affiliation: Department of Immunology, Monash University, Melbourne, Australia.
authors.forename: C L
authors.initials: CL
authors.lastname: Hardy
authors.forename: A E
authors.initials: AE
authors.lastname: O'Connor
authors.forename: J
authors.initials: J
authors.lastname: Yao
authors.forename: K
authors.initials: K
authors.lastname: Sebire
authors.forename: D M
authors.initials: DM
authors.lastname: de Kretser
authors.forename: J M
authors.initials: JM
authors.lastname: Rolland
authors.forename: G P
authors.initials: GP
authors.lastname: Anderson
authors.forename: D J
authors.initials: DJ
authors.lastname: Phillips
authors.forename: R E
authors.initials: RE
authors.lastname: O'Hehir
mesh_terms: D028341:Activins / Q000378:metabolism*; D000818:Animals; D001249:Asthma / Q000276:immunology / Q000378:metabolism*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D004195:Disease Models, Animal; D005260:Female; D038681:Follistatin / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D007114:Immunization; D007378:Interleukins / Q000096:biosynthesis; D008168:Lung / Q000378:metabolism; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009093:Mucus / Q000378:metabolism; D010047:Ovalbumin / Q000276:immunology; D011994:Recombinant Proteins / Q000494:pharmacology; D018418:Th2 Cells / Q000276:immunology
chemical_list: D038681:Follistatin; D007378:Interleukins; D011994:Recombinant Proteins; C422405:activin A; D028341:Activins; D010047:Ovalbumin