Increased TGF- beta 2 in severe asthma with eosinophilia

• Published in: Journal of Allergy and Clinical Immunology Vol. 115; no. 1; pp. 110 - 117
• Main Authors: Balzar, S, Chu, H W, Silkoff, P, Cundall, M, Trudeau, J B, Strand, M, Wenzel, S
• Format: Journal Article
• Language: English
• Published: 01.01.2005
• ISSN: 0091-6749; 1365-2567
• 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- beta 1, TGF- beta 2, and TGF- beta 3) 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- beta 2 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- beta 2. 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- beta 2, 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.