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J Allergy Clin Immunol. 2005 Jan;115(1):110-7.

Increased TGF-beta2 in severe asthma with eosinophilia.

Author information

1
Department of Medicine, National Jewish Medical and Research Center and University of Colorado Health Sciences Center, Denver 80206, USA. balzars@njc.org

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.

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.

PMID:
15637555
DOI:
10.1016/j.jaci.2004.09.034
[Indexed for MEDLINE]
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