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JCI table of contents: Oct. 18, 2007
Date:10/18/2007

EDITOR'S PICK: New links in the cystic fibrosis chain uncover potential therapeutics

Cystic fibrosis (CF) is an inherited disease caused by mutations in the CFTR gene. Each mutation has number of effects on the cells of the lungs. New evidence generated in vitro by Vojo Deretic and colleagues at the University of New Mexico School of Medicine, Albuquerque, has provided insight into the mechanisms by which one of these changes impacts both CF and the complications of CF. These data provide support for ongoing clinical trials and raise the possibility of new targets for the development of drugs to treat individuals with CF.

CFTR mutations that cause CF make a compartment of the cell known as the TGN more acidic than it is in cells from healthy individuals. In this study, in vitro analysis revealed that hyperacidification of the TGN causes increased activity of a protein known as furin. Through increased production of a soluble factor known as TGF-beta this augmented the production of collagen (which in situ is associated with tissue fibrosis, a characteristic of damaged lung in individuals with CF) and suppressed the ability of human macrophages to kill the bacterium Pseudomonas aeruginosa, infection with which is a major complication for individuals with CF. This study provides strong support for the use of chloroquine (which counteracts high levels of TGN acidity) to treat CF, something that is currently being tested in clinical trials, and identifies furin inhibitors as potential new therapeutics for the treatment of CF.

TITLE: Elevated furin levels in human cystic fibrosis cells result in hypersusceptibility to exotoxin A-induced cytotoxicity

AUTHOR CONTACT:

Vojo Deretic
University of New Mexico School of Medicine, Albuquerque, New Mexico, USA.
Phone: (505) 272-0291; Fax: (505) 272-5309; E-mail: vderetic@salud.unm.edu.

View the PDF of this article at
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Contact: Karen Honey
press_releases@the-jci.org
215-573-1850
Journal of Clinical Investigation
Source:Eurekalert

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