Increased TGF-[beta]2 in severe asthma with eosinophilia

Background Airway eosinophilia and thickened subepithelial basement membrane have previously been reported to increase with increases in TGF-β expression. However, little is known regarding the expression of specific TGF-β isoforms (TGF-β1, TGF-β2, and TGF-β3) in asthma, despite recent evidence suggesting that isoforms may have differing biologic activities. Objective This study examined airway tissue expression of the 3 TGF-β 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-β isoforms, their receptors, collagen I deposition, connective tissue growth factor expression, and tissue inhibitor of metalloproteinases 1 levels. Results Of the isoforms, only TGF-β2 was different among the groups and increased in severe asthma (overallP< .0001). The increase was due to severe asthma tissue eosinophils which, unlike eosinophils in other groups, expressed high amounts of TGF-β2. Subjects with severe asthma also had the thickest subbasement membrane and highest tissue inhibitor of metalloproteinases 1 levels. In contrast, TGF-β receptor 1 and connective tissue growth factor were both consistently downregulated in asthma, regardless of severity. Conclusion TGF-β2, expressed mainly by eosinophils, is the predominant isoform expressed in severe asthma, and is associated with increased profibrotic responses. Decreased expression of TGF-β receptor 1 and connective tissue growth factor in all asthma severity groups suggests a degree of activation of the TGF-β pathway in airway tissue of all asthmatic compared with normal airways.