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. 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. 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. Of the isoforms, only TGF-β2 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-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. 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.
Balzar, S., Chu, H. W., Silkoff, P., Cundall, M., Trudeau, J. B., Strand, M., & Wenzel, S. (2005). Increased TGF-β2 in severe asthma with eosinophilia. Journal of Allergy and Clinical Immunology, 115(1), 110–117. https://doi.org/10.1016/j.jaci.2004.09.034