title: Increased TGF-beta2 in severe asthma with eosinophilia.
abstract: BACKGROUND
  Airway eosinophilia and thickened subepithelial basement membrane have previously been reported to increase with increases in TGF-beta expression. However, little is known regarding the expression of specific TGF-beta isoforms (TGF-beta1, TGF-beta2, and TGF-beta3) in asthma, despite recent evidence suggesting that isoforms may have differing biologic activities.
  
  
  OBJECTIVE
  This study examined airway tissue expression of the 3 TGF-beta isoforms and several downstream pathway elements in 48 patients with severe asthma with or without persistent eosinophilia, 14 patients with mild asthma, and 21 normal subjects.
  
  
  METHODS
  Immunochemistry/immunofluorescence, quantitative real-time PCR and enzyme immunoassay were used to evaluate the 3 TGF-beta isoforms, their receptors, collagen I deposition, connective tissue growth factor expression, and tissue inhibitor of metalloproteinases 1 levels.
  
  
  RESULTS
  Of the isoforms, only TGF-beta2 was different among the groups and increased in severe asthma (overall P < .0001). The increase was due to severe asthma tissue eosinophils which, unlike eosinophils in other groups, expressed high amounts of TGF-beta2. Subjects with severe asthma also had the thickest subbasement membrane and highest tissue inhibitor of metalloproteinases 1 levels. In contrast, TGF-beta receptor 1 and connective tissue growth factor were both consistently downregulated in asthma, regardless of severity.
  
  
  CONCLUSIONS
  TGF-beta2, expressed mainly by eosinophils, is the predominant isoform expressed in severe asthma, and is associated with increased profibrotic responses. Decreased expression of TGF-beta receptor 1 and connective tissue growth factor in all asthma severity groups suggests a degree of activation of the TGF-beta pathway in airway tissue of all asthmatic compared with normal airways.
authors.affiliation: Department of Medicine, National Jewish Medical and Research Center and University of Colorado Health Sciences Center, Denver 80206, USA. balzars@njc.org
authors.forename: Silvana
authors.initials: S
authors.lastname: Balzar
authors.forename: Hong Wei
authors.initials: HW
authors.lastname: Chu
authors.forename: Phillip
authors.initials: P
authors.lastname: Silkoff
authors.forename: Meghan
authors.initials: M
authors.lastname: Cundall
authors.forename: John B
authors.initials: JB
authors.lastname: Trudeau
authors.forename: Matthew
authors.initials: M
authors.lastname: Strand
authors.forename: Sally
authors.initials: S
authors.lastname: Wenzel
mesh_terms: D000328:Adult; D001249:Asthma / Q000276:immunology* / Q000378:metabolism; D001980:Bronchi / Q000276:immunology; D003238:Connective Tissue / Q000378:metabolism; D004802:Eosinophilia / Q000276:immunology* / Q000378:metabolism; D004804:Eosinophils / Q000378:metabolism; D005260:Female; D006133:Growth Substances / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009130:Muscle, Smooth / Q000276:immunology; D020033:Protein Isoforms / Q000032:analysis / Q000096:biosynthesis; D012333:RNA, Messenger / Q000032:analysis; D018125:Receptors, Transforming Growth Factor beta / Q000032:analysis / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000032:analysis / Q000096:biosynthesis*; D053781:Transforming Growth Factor beta2
chemical_list: D006133:Growth Substances; D020033:Protein Isoforms; D012333:RNA, Messenger; D018125:Receptors, Transforming Growth Factor beta; C509041:TGFB2 protein, human; D016212:Transforming Growth Factor beta; D053781:Transforming Growth Factor beta2