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Chloroquine normalizes aberrant transforming growth factor beta activity in cystic fibrosis bronchial epithelial cells

Identifieur interne : 001E12 ( Main/Merge ); précédent : 001E11; suivant : 001E13

Chloroquine normalizes aberrant transforming growth factor beta activity in cystic fibrosis bronchial epithelial cells

Auteurs : Elizabeth A. Perkett [États-Unis] ; Wojclech Ornatowski [États-Unis] ; Jens F. Poschet [États-Unis] ; Vojo Deretic [États-Unis]

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RBID : Pascal:06-0360316

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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-p) 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-p produced by CF and normal cells was measured using a reporter cell line with a TGF-p 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-p levels.

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Pascal:06-0360316

Le document en format XML

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<term>Activity</term>
<term>Anomaly</term>
<term>Antimalarial</term>
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<term>Chloroquine</term>
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<term>Cystic fibrosis</term>
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<term>Mucoviscidose</term>
<term>Appareil respiratoire pathologie</term>
<term>Chloroquine</term>
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<div type="abstract" xml:lang="en">Cystic fibrosis (CF) remains a fatal progressive disease in spite of the discovery and characterization of the CFTR gene. Transforming growth factor beta (TGF-p) 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-p produced by CF and normal cells was measured using a reporter cell line with a TGF-p 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-p levels.</div>
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