Responsiveness of human bronchial fibroblasts and epithelial cells from asthmatic and non-asthmatic donors to the transforming growth factor-β1 in epithelial-mesenchymal trophic unit model

Abstract

Background: Asthma-related airway wall remodeling is associated with i.a. damage of bronchial epithelium and subepithelial fibrosis. Functional interactions between human bronchial epithelial cells and human bronchial fibroblasts are known as the epithelial-mesenchymal trophic unit (EMTU) and are necessary for a proper functioning of lung tissue. However, a high concentration of the transforming growth factor-β 1 (TGF-β 1 ) in the asthmatic bronchi drives the structural disintegrity of epithelium with the epithelial-to-mesenchymal transition (EMT) of the bronchial epithelial cells, and of subepitheial fibrosis with the fibroblast-to-myofibroblast transition (FMT) of the bronchial fibroblasts. Since previous reports indicate different intrinsic properties of the human bronchial epithelial cells and the human bronchial fibroblasts which affect their EMT/FMT potential beetween cells derived from asthmatic and non-asthmatic patients, cultured separatelly in vitro , we were interested to see whether corresponding effects could be obtained in co-cultures of bronchial epithelial cells and bronchial fibroblasts. In this study, we investigate the effects of the TGF-β 1 on the EMT markers of the bronchial epithelial cells cultured in the air-liquid-interface and effectiveness of FMT in the bronchial fibroblast populations in the EMTU models. Results: Our results show that the asthmatic co-cultures are more sensitive to the TGF-β 1 than the non-asthmatic ones, which is associated with a higher potential of asthmatic bronchial cells for a profibrotic response, analogously to be observed in “2D” cultures. Moreover, our results indicate a noticeable impact of human bronchial epithelial cells on the TGF-β 1 -induced FMT, stronger in the asthmatic bronchial fibroblast populations in comparison to the non-asthmatic ones. Conclusions: Our data are the first to demonstrate a protective effect of human bronchial fibroblasts on the properties of human bronchial epithelial cells, which suggests that intrinsic properties of not only epithelium but also subepithelial fibroblasts affect a proper condition and function of the EMTU in both normal and asthmatic individuals.