Cystic fibrosis (CF) remains a fatal progressive disease in spite of the discovery and characterization of the CFTR gene. Transforming growth factor beta (TGF-β) has been implicated in pathophysiology of CF. Previous reports have shown the trans-Golgi network (TGN) is hyperacdified in CF epithelial cells in culture and that this hyperacidification can be corrected with the membrane permeant weak base, chloroquine. In this study bioactive TGF-β produced by CF and normal cells was measured using a reporter cell line with a TGF-β responsive promoter linked to luciferase. Increased levels of TGF-β were detected in the conditioned media from CF epithelial cells compared to their matched controls—(IB3-1 vs. S9; pCEP-R vs. pCEP, CuFi-4 vs. NuLi-1). Levels of TGF-β were normalized with chloroquine indicating that the hyperacidification of the TGN of CF cells is responsible for the altered TGF-β levels. Pediatr Pulmonol. 2006; 41:771-778.
© 2006 Wiley-Liss, Inc.