Transforming growth factor β1 gene expression in human airways

Abstract

Background - Asthmatic airways have a characteristic deposition of connective tissue under the epithelial basement membrane, but the mediators involved in this alteration are unknown. Several authors have postulated that transforming growth factor β1 (TGF-β1) could be overexpressed in asthmatic airways. Methods - Lung samples from 16 asthmatic patients, six patients with chronic obstructive pulmonary disease (COPD), and six non-obstructed smokers were analysed. RNA was extracted from these tissues to measure expression of TGF-β1 by Northern blot analysis using a cDNA probe for TGF-β1. The level of expression was quantitated by densitometry using glyceraldehyde 3-phosphate dehydrogenase mRNA as a control. TGF-β1 was localised to specific cell types in these lungs by immunohistochemical analysis using polyclonal antibodies specific for intracellular and extracellular TGF-β1. Results - The 2.5 kb TGF-β1 mRNA was seen in all 18 samples analysed by Northern blotting and densitometric analysis showed no difference between the asthmatic group (mean (SD) 108% (43%)), the group with COPD (122% (33%)), and the non-obstructed group (100% (49%)). The TGF-β1 precursor was immunolocalised throughout the airway wall including the epithelium and in alveolar macrophages. The mature TGF-β1 was localised primarily within the connective tissue of the airway wall. These patterns of expression of both forms of TGF-β1 were similar in lungs from asthmatic patients, those with COPD, and controls. Conclusions - While TGF-β1 mRNA and protein are abundantly expressed in human lungs, there is no clear difference in expression between the airways of asthmatic subjects and those of smokers with and without COPD.