Reticular Basement Membrane Remodelling Regulates Bronchial Epithelial Attachment, Barrier Integrity and Inflammatory Signalling in Asthma.

Asthma is characterized by persistent airway epithelial dysfunction and remodelling of the reticular basement membrane (RBM). In healthy airways, the RBM is primarily composed of the extracellular matrix (ECM) proteins laminin and collagen-IV, but in remodelled asthmatic airways, the RBM has increased deposition of collagen-I, -III and fibronectin. Here, we systematically compared the effects of collagen-I, -III, -IV, fibronectin, laminin, and bovine serum albumin (BSA) control on bronchial epithelial cells (BECs) from six healthy controls and seven individuals with asthma. Epithelial attachment, spreading and barrier function were assessed in real time over 72 h using electrical cell-substrate impedance sensing. Cell culture supernatants were analyzed for release of epithelial cytokines, thymic stromal lymphopoietin (TSLP), interleukin (IL)-6, IL-8, and IL-11 using ELISA. BECs from both control and asthma donors had faster cell attachment, spreading, and barrier formation on collagen-I, -III, -IV, and fibronectin compared to laminin and BSA. BECs from both control and asthma donors cultured on collagen -I and -III produced more TSLP, but had no effect on IL-6, IL-8, and IL-11 expression. In summary, remodelling of the RBM in asthma may promote epithelial barrier formation whilst simultaneously enhancing epithelial-derived Th2 inflammation through increased TSLP release.