Abstract
BackgroundThe asthma-related airway wall remodeling is associated i.a. with 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-β1 (TGF-β1) in the asthmatic bronchi drives the structural disintegrity of epithelium with the epithelial-to-mesenchymal transition (EMT) of the bronchial epithelial cells, and of subepithelial 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 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 a co-culture of the bronchial epithelial cells and bronchial fibroblasts. In this study, we investigate the effects of the TGF-β1 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.ResultsOur results show that the asthmatic co-cultures are more sensitive to the TGF-β1 than the non-asthmatic ones, which is associated with a higher potential of the asthmatic bronchial cells for a profibrotic response, analogously to be observed in '2D' cultures. They also indicate a noticeable impact of human bronchial epithelial cells on the TGF-β1-induced FMT, stronger in the asthmatic bronchial fibroblast populations in comparison to the non-asthmatic ones. Moreover, our results suggest the protective effects of fibroblasts on the structure of the TGF-β1–exposed mucociliary differentiated bronchial epithelial cells and their EMT potential.ConclusionsOur data are the first to demonstrate a protective effect of the human bronchial fibroblasts on the properties of the 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.
Highlights
The asthma-related airway wall remodeling is associated i.a. with a damage of bronchial epithelium and subepithelial fibrosis
Our data are the first to demonstrate a protective effect of the human bronchial fibroblasts on the properties of the human bronchial epithelial cells, which suggests that intrinsic properties of epithelium and subepithelial fibroblasts affect a proper condition and function of the epithelial-mesenchymal trophic unit (EMTU) in both normal and asthmatic individuals
To clarify whether this phenomenon is pronounced in the EMTU model, firstly, we checked in this study if the medium dedicated for the air-liquid-interface (ALI) and EMTU cultures significantly affects the fibroblast-to-myofibroblast transition (FMT) potential of the transforming growth factor-β1 (TGF-β1)-treated human bronchial fibroblasts (HBFs)
Summary
The asthma-related airway wall remodeling is associated i.a. with a damage of bronchial epithelium and subepithelial fibrosis. The activated mesenchymal cells establish secretory feedback mechanisms and affect the airway epithelium Based on these observations Holgate created a concept that the impairment of the barrier function of the airway epithelium plays a central role in the progression of the airway remodeling and asthma symptoms [12]. The epithelium derived from asthmatic donors is characterized by an enhanced expression of inflammatory- and remodelingrelated genes in comparison to the ones obtained from non-asthmatic donors [13, 15] These intrinsic properties of the asthmatic airway epithelial cells affect the profibrogenic potential of the airway fibroblasts [16,17,18,19]
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