title: Expression of growth factors by airway epithelial cells in a model of chronic asthma: regulation and relationship to subepithelial fibrosis.
abstract: BACKGROUND
  Growth factors produced by airway epithelial cells may be important in the pathogenesis of subepithelial fibrosis, a distinctive lesion of chronic human asthma.
  
  
  OBJECTIVE
  To examine the relationship between the development of subepithelial fibrosis and the expression of transforming growth factor-beta 1 (TGF-beta 1) and ligands for the epidermal growth factor receptor.
  
  
  METHODS
  BALB/c mice sensitized to ovalbumin were chronically challenged by inhalation of low levels of antigen, leading to development of subepithelial fibrosis and other changes of airway wall remodelling. Growth factor expression was assessed by immunohistochemistry and enzyme immunoassay.
  
  
  RESULTS
  Allergic sensitization directly correlated with airway epithelial expression of both the cleaved, potentially biologically active form of TGF-beta 1 and of amphiregulin in response to allergen challenge. Accumulation of TGF-beta 1 was related to remodelling of the airway wall in chronic asthma, whereas expression of amphiregulin did not exhibit a similar relationship. Production of epithelial cell-derived TGF-beta 1 appeared to be regulated by IL-13, while both IL-13 and CD4(+) T cells regulated accumulation of TGF-beta 1. In contrast to results reported in high-level exposure models of airway fibrosis, eosinophils did not appear to be a significant source of TGF-beta 1.
  
  
  CONCLUSIONS
  Airway epithelial cell-derived TGF-beta 1 has a potentially crucial role in the development of airway wall remodelling in asthma. Immunological mechanisms may regulate the release and accumulation of TGF-beta 1.
authors.affiliation: Department of Pathology, University of New South Wales, Sydney, Australia. R.Kumar@unsw.edu.au
authors.forename: R K
authors.initials: RK
authors.lastname: Kumar
authors.forename: C
authors.initials: C
authors.lastname: Herbert
authors.forename: P S
authors.initials: PS
authors.lastname: Foster
mesh_terms: D000485:Allergens / Q000276:immunology; D066258:Amphiregulin; D000818:Animals; D001249:Asthma / Q000276:immunology / Q000378:metabolism*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002908:Chronic Disease; D004195:Disease Models, Animal; D066255:EGF Family of Proteins; D004815:Epidermal Growth Factor / Q000378:metabolism; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D005260:Female; D005355:Fibrosis; D006023:Glycoproteins / Q000096:biosynthesis*; D007124:Immunoenzyme Techniques; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis*; D018793:Interleukin-13 / Q000276:immunology; D008024:Ligands; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology; D020545:Respiratory Mucosa / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D014132:Trachea / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000096:biosynthesis*; D053773:Transforming Growth Factor beta1
chemical_list: C587848:AREG protein, human; D000485:Allergens; D066258:Amphiregulin; C587849:Areg protein, mouse; D066255:EGF Family of Proteins; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D018793:Interleukin-13; D008024:Ligands; C508960:TGFB1 protein, human; C508961:Tgfb1 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D004815:Epidermal Growth Factor; D010047:Ovalbumin