title: Role of insulin-like growth factor binding protein-3 in allergic airway remodeling.
abstract: BACKGROUND
  The hallmarks of allergic asthma are airway inflammation, obstruction, and remodeling. Airway remodeling may lead to irreversible airflow obstruction with increased morbidity and mortality. Despite advances in the treatment of asthma, the mechanisms underlying airway remodeling are still poorly understood. We reported that insulin-like growth factor (IGF) binding proteins (IGFBPs) contribute to extracellular matrix deposition in idiopathic pulmonary fibrosis; however, their contribution to airway remodeling in asthma has not been established.
  
  
  OBJECTIVE
  We hypothesized that IGFBP-3 is overexpressed in asthma and contributes to airway remodeling.
  
  
  METHODS
  We evaluated levels of IGFBP-3 in tissues and bronchoalveolar lavage fluid from patients with asthma at baseline and 48 hours after allergen challenge, in reparative epithelium in an in vitro wounding assay, and in conditioned media from cytokine- and growth factor-stimulated primary epithelial cells.
  
  
  RESULTS
  IGFBP-3 levels and distribution were evaluated by Western blot, ELISA, and immunofluorescence. IGFBP-3 is increased in vivo in the airway epithelium of patients with asthma compared with normal control subjects. The concentration of IGFBP-3 is increased in the bronchoalveolar lavage fluid of patients with asthma after allergen challenge, its levels are increased in reparative epithelium in an in vitro wounding assay and in the conditioned medium of primary airway epithelial cell cultures stimulated with IGF-I.
  
  
  CONCLUSIONS
  Our results suggest that one mechanism of allergic airway remodeling is through the secretion of the profibrotic IGFBP-3 from IGF-I-stimulated airway epithelial cells during allergic inflammation.
authors.affiliation: Department of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA.
authors.forename: Kristen L
authors.initials: KL
authors.lastname: Veraldi
authors.forename: Bethany T
authors.initials: BT
authors.lastname: Gibson
authors.forename: Hidekata
authors.initials: H
authors.lastname: Yasuoka
authors.forename: Michael M
authors.initials: MM
authors.lastname: Myerburg
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Kelly
authors.forename: Silvana
authors.initials: S
authors.lastname: Balzar
authors.forename: Nizar N
authors.initials: NN
authors.lastname: Jarjour
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Pilewski
authors.forename: Sally E
authors.initials: SE
authors.lastname: Wenzel
authors.forename: Carol A
authors.initials: CA
authors.lastname: Feghali-Bostwick
mesh_terms: D000328:Adult; D001249:Asthma / Q000276:immunology / Q000378:metabolism*; D015153:Blotting, Western; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism; D005260:Female; D005355:Fibrosis; D005455:Fluorescent Antibody Technique; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000096:biosynthesis* / Q000276:immunology; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012130:Respiratory Hypersensitivity / Q000276:immunology / Q000378:metabolism; D012720:Severity of Illness Index
chemical_list: D018972:Insulin-Like Growth Factor Binding Protein 3