title: Chloroquine normalizes aberrant transforming growth factor beta activity in cystic fibrosis bronchial epithelial cells.
abstract: Cystic fibrosis (CF) remains a fatal progressive disease in spite of the discovery and characterization of the CFTR gene. Transforming growth factor beta (TGF-beta) 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-beta produced by CF and normal cells was measured using a reporter cell line with a TGF-beta responsive promoter linked to luciferase. Increased levels of TGF-beta 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-beta were normalized with chloroquine indicating that the hyperacidification of the TGN of CF cells is responsible for the altered TGF-beta levels.
authors.affiliation: Department of Pediatrics, University of New Mexico Health Sciences Center, Albuquerque, New Mexico 87131-0001, USA. eperkett@salud.unm.edu
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Perkett
authors.forename: Wojciech
authors.initials: W
authors.lastname: Ornatowski
authors.forename: Jens F
authors.initials: JF
authors.lastname: Poschet
authors.forename: Vojo
authors.initials: V
authors.lastname: Deretic
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001980:Bronchi / Q000166:cytology*; D002478:Cells, Cultured; D002738:Chloroquine / Q000494:pharmacology*; D017077:Culture Media, Conditioned; D003550:Cystic Fibrosis / Q000097:blood / Q000503:physiopathology*; D004847:Epithelial Cells / Q000378:metabolism*; D006801:Humans; D008168:Lung / Q000166:cytology*; D016212:Transforming Growth Factor beta / Q000097:blood*; D021601:trans-Golgi Network / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D017077:Culture Media, Conditioned; D016212:Transforming Growth Factor beta; D002738:Chloroquine