RT Journal Article
SR Electronic
T1 Regulation of corticosteroid binding globulin (CBG) in the inflammatory context of cystic fibrosis
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP 366
VO 38
IS Suppl 55
A1 Jessica Taytard
A1 Carine Rebeyrol
A1 Dominique Debray
A1 Annick Clement
A1 Nicolas Chignard
A1 Philippe Le Rouzic
YR 2011
UL http://erj.ersjournals.com/content/38/Suppl_55/366.abstract
AB Background: Cystic Fibrosis (CF) is characterised by chronic lung inflammation. In CF, glucocorticoids (GC) are a widely used therapeutic tool. However, their efficiency, and the benefit/risk ratio are still discussed. In plasma, 90% of GC is bound to the chaperone protein CBG which regulates its bio-disponibility. CBG is mainly produced by the liver. Recent works enlightened the fact that, more than a simple carrier protein, CBG could also address GC specifically to the inflammation site, thereby modulating the response to GC in an inflammatory context.Objectives: Study the expression and regulation of CBG in the liver and assess its pulmonary expression in the inflammatory context of CF.Methods: Hepatic levels of CBG:Biopsies from healthy donors, cirrhotic CF and non CF patients: measure of the transcripts levels of CBG and interleukin-6.Hepatocarcinoma derived cell-lines Hep3B and HepG2: regulation of CBG expression.Lung levels of CBG:Lung biopsies; expression of CBGBronchial epithelial cell lines; regulation of CBG expressionResults: We show an increase in CBG expression:in the liver and lung of CF patients.in the hepatic and lung cell lines in an inflammatory context.GC has no effects on CBG expression in hepatic cell lines, but increases CBG levels in the lung cell lines.Discussion: We show stimulation of the expression of CBG in the inflammatory context of CF. Comparative results from hepatic and lung cell lines enlight a different regulation of CBG expression. Overall, increase in CBG expression in CF could mean initially a decrease in GC bio-disponibility but, ultimately, an enhanced corticosteroid half life and possible prolonged effects.