Increased TGF-beta2 in severe asthma with eosinophilia

J Allergy Clin Immunol. 2005 Jan;115(1):110-7. doi: 10.1016/j.jaci.2004.09.034.


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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Asthma / immunology*
  • Asthma / metabolism
  • Bronchi / immunology
  • Connective Tissue / metabolism
  • Eosinophilia / immunology*
  • Eosinophilia / metabolism
  • Eosinophils / metabolism
  • Female
  • Growth Substances / metabolism
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Muscle, Smooth / immunology
  • Protein Isoforms / analysis
  • Protein Isoforms / biosynthesis
  • RNA, Messenger / analysis
  • Receptors, Transforming Growth Factor beta / analysis
  • Receptors, Transforming Growth Factor beta / metabolism
  • Transforming Growth Factor beta / analysis
  • Transforming Growth Factor beta / biosynthesis*
  • Transforming Growth Factor beta2


  • Growth Substances
  • Protein Isoforms
  • RNA, Messenger
  • Receptors, Transforming Growth Factor beta
  • TGFB2 protein, human
  • Transforming Growth Factor beta
  • Transforming Growth Factor beta2