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Opposite Expression of Hepatic and Pulmonary Corticosteroid-Binding Globulin in Cystic Fibrosis Patients

Authors :
Anastasia Tchoukaev
Jessica Taytard
Nathalie Rousselet
Carine Rebeyrol
Dominique Debray
Sabine Blouquit-Laye
Marie-Pierre Moisan
Aline Foury
Loic Guillot
Harriet Corvol
Olivier Tabary
Philippe Le Rouzic
Centre de Recherche Saint-Antoine (CR Saint-Antoine)
Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP]
Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
CHU Trousseau [APHP]
Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
CHU Necker - Enfants Malades [AP-HP]
Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Infection et inflammation (2I)
Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Nutrition et Neurobiologie intégrée (NutriNeuro)
Université Bordeaux Segalen - Bordeaux 2-Institut National de la Recherche Agronomique (INRA)-Université Sciences et Technologies - Bordeaux 1-Institut Polytechnique de Bordeaux-Ecole nationale supérieure de chimie, biologie et physique
Mucoviscidose: physiopathologie et phénogénomique [CRSA]
Centre de Recherche Saint-Antoine (CRSA)
Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)
Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)
Service de Pneumologie pédiatrique [CHU Trousseau]
Université Bordeaux Segalen - Bordeaux 2-Institut National de la Recherche Agronomique (INRA)-Université Sciences et Technologies - Bordeaux 1 (UB)-Institut Polytechnique de Bordeaux-Ecole nationale supérieure de chimie, biologie et physique
Sorbonne Université - Faculté de Médecine (SU FM)
Sorbonne Université (SU)
ProdInra, Migration
Source :
Frontiers in Pharmacology, Frontiers in Pharmacology, Frontiers, 2018, 9, pp.1-9. ⟨10.3389/fphar.2018.00545⟩, Frontiers in Pharmacology, Vol 9 (2018), Frontiers in Pharmacology, 2018, 9, pp.1-9. ⟨10.3389/fphar.2018.00545⟩, Frontiers in Pharmacology (9), 1-9. (2018)
Publication Year :
2018
Publisher :
Frontiers Media SA, 2018.

Abstract

International audience; 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 H-3-cortisol and the measurement of the elastase/alpha 1-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.

Details

ISSN :
16639812
Volume :
9
Database :
OpenAIRE
Journal :
Frontiers in Pharmacology
Accession number :
edsair.doi.dedup.....dfe37131072eecc71843602671c7aac0
Full Text :
https://doi.org/10.3389/fphar.2018.00545