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Opposite Expression of Hepatic and Pulmonary Corticosteroid-Binding Globulin in Cystic Fibrosis Patients
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 g...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5996105/ https://www.ncbi.nlm.nih.gov/pubmed/29922157 http://dx.doi.org/10.3389/fphar.2018.00545 |
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author | Tchoukaev, Anastasia Taytard, Jessica Rousselet, Nathalie Rebeyrol, Carine Debray, Dominique Blouquit-Laye, Sabine Moisan, Marie-Pierre Foury, Aline Guillot, Loic Corvol, Harriet Tabary, Olivier Le Rouzic, Philippe |
author_facet | Tchoukaev, Anastasia Taytard, Jessica Rousselet, Nathalie Rebeyrol, Carine Debray, Dominique Blouquit-Laye, Sabine Moisan, Marie-Pierre Foury, Aline Guillot, Loic Corvol, Harriet Tabary, Olivier Le Rouzic, Philippe |
author_sort | Tchoukaev, Anastasia |
collection | PubMed |
description | 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 (3)H-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. |
format | Online Article Text |
id | pubmed-5996105 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-59961052018-06-19 Opposite Expression of Hepatic and Pulmonary Corticosteroid-Binding Globulin in Cystic Fibrosis Patients Tchoukaev, Anastasia Taytard, Jessica Rousselet, Nathalie Rebeyrol, Carine Debray, Dominique Blouquit-Laye, Sabine Moisan, Marie-Pierre Foury, Aline Guillot, Loic Corvol, Harriet Tabary, Olivier Le Rouzic, Philippe Front Pharmacol Pharmacology 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 (3)H-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. Frontiers Media S.A. 2018-06-05 /pmc/articles/PMC5996105/ /pubmed/29922157 http://dx.doi.org/10.3389/fphar.2018.00545 Text en Copyright © 2018 Tchoukaev, Taytard, Rousselet, Rebeyrol, Debray, Blouquit-Laye, Moisan, Foury, Guillot, Corvol, Tabary and Le Rouzic. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Pharmacology Tchoukaev, Anastasia Taytard, Jessica Rousselet, Nathalie Rebeyrol, Carine Debray, Dominique Blouquit-Laye, Sabine Moisan, Marie-Pierre Foury, Aline Guillot, Loic Corvol, Harriet Tabary, Olivier Le Rouzic, Philippe Opposite Expression of Hepatic and Pulmonary Corticosteroid-Binding Globulin in Cystic Fibrosis Patients |
title | Opposite Expression of Hepatic and Pulmonary Corticosteroid-Binding Globulin in Cystic Fibrosis Patients |
title_full | Opposite Expression of Hepatic and Pulmonary Corticosteroid-Binding Globulin in Cystic Fibrosis Patients |
title_fullStr | Opposite Expression of Hepatic and Pulmonary Corticosteroid-Binding Globulin in Cystic Fibrosis Patients |
title_full_unstemmed | Opposite Expression of Hepatic and Pulmonary Corticosteroid-Binding Globulin in Cystic Fibrosis Patients |
title_short | Opposite Expression of Hepatic and Pulmonary Corticosteroid-Binding Globulin in Cystic Fibrosis Patients |
title_sort | opposite expression of hepatic and pulmonary corticosteroid-binding globulin in cystic fibrosis patients |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5996105/ https://www.ncbi.nlm.nih.gov/pubmed/29922157 http://dx.doi.org/10.3389/fphar.2018.00545 |
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