Exploring GPCR activation of CFTR in model human airway cell lines

Abstract

Introduction: Cystic Fibrosis is a genetic disease caused by mutations in the gene encoding the CFTR (cystic fibrosis transmembrane conductance regulator) protein. The disease causes respiratory and digestive complications. CFTR protein activity can be modulated through GPCR (G protein-coupled receptor) signaling pathways. However, in vitro models for studying GPCR-mediated CFTR activation are not well-established. In this study, we investigated the potential utility of widely available model airway epithelial cell lines to study GPCR-mediated CFTR regulation. Methods: We cultured wild-type and F508del-CFTR human bronchial epithelial (HBE). Using Ussing chambers, we examined the effects of prostaglandin ligands on CFTR-mediated chloride transport. Results: Prostaglandin receptors were expressed in 16HBE cells. Application of prostaglandin ligands resulted in activation of CFTR-mediated ion transport. Conclusion: Prostaglandin ligand treatment enhanced CFTR function, consistent with presence of prostaglandin receptor expression in the tested cell lines. Further research is needed to characterize the cell type-specific responses to prostaglandin ligands and their effects on CFTR activation.Lew Wentz FoundationIntegrative Biolog