Abstract
Cystic fibrosis (CF) is characterized by a chronic pulmonary inflammation. In CF, glucocorticoids (GC) are widely used, but their efficacy and benefit/risk ratio are still debated. In plasma, corticosteroid-binding globulin (CBG) binds 90% of GC and delivers them to the inflammatory site. The main goal of this work was to study CBG expression in CF patients in order to determine whether CBG could be used to optimize GC treatment. The expression of CBG was measured in liver samples from CF cirrhotic and non-CF cirrhotic patients by qPCR and Western blot and in lung samples from non-CF and CF patients by qPCR. CBG binding assays with 3H-cortisol and the measurement of the elastase/α1-antitrypsin complex were performed using the plasmas. CBG expression increased in the liver at the transcript and protein level but not in the plasma of CF patients. This is possibly due to an increase of plasmatic elastase. We demonstrated that pulmonary CBG was expressed in the bronchi and bronchioles and its expression decreased in the CF lungs, at both levels studied. Despite the opposite expression of hepatic and pulmonary CBG in CF patients, the concentration of CBG in the plasma was normal. Thus, CBG might be useful to deliver an optimized synthetic GC displaying high affinity for CBG to the main inflammatory site in the context of CF, e.g., the lung.
Highlights
Cystic fibrosis (CF) is the most frequent autosomal recessive genetic disorder among the Caucasian population
To assess if the increase in corticosteroid-binding globulin (CBG) in the liver of CF patients resulted in an increase in the protein release into the plasma, we measured the concentration of CBG in the plasma of CF and nonCF patients using a binding assay with concanavalin A-sepharose
CBG was never studied in this context, even though it could lead to the optimization of GC treatment for CF patients
Summary
Cystic fibrosis (CF) is the most frequent autosomal recessive genetic disorder among the Caucasian population. This disease is caused by mutations in the CFTR gene (Cystic Fibrosis Transmembrane conductance Regulator) which encodes a chloride channel (Riordan et al, 1989). Due to the wide expression of CFTR, CF is a multi-organ disease, affecting the lungs, the liver, the digestive tract, the pancreas, the reproductive tract and the sweat glands. CFTR is expressed at the apical membrane of the cholangiocytes (Cohn et al, 1993). This, in turn, causes inflammation and collagen deposition around the bile ducts and portal tracts, leading to focal biliary and periportal fibrosis, which can progress to multilobular
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
