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

Autor: 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
Přispěvatelé: 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
Rok vydání: 2018
Předmět:
0301 basic medicine
medicine.medical_specialty
corticosteroid-binding globulin
cystic fibrosis
glucocorticoids
liver
lung
Globulin
[SDV]Life Sciences [q-bio]
Context (language use)
[SDV.GEN] Life Sciences [q-bio]/Genetics
[SDV.GEN.GA] Life Sciences [q-bio]/Genetics/Animal genetics
Cystic fibrosis
03 medical and health sciences
0302 clinical medicine
pcr
Western blot
Transcortin
glucocorticoïde
Internal medicine
Medicine
Pharmacology (medical)
mucoviscidose
corticostéroïde plasmique
fibrose cystique
Pharmacology
[SDV.GEN]Life Sciences [q-bio]/Genetics
Lung
biology
medicine.diagnostic_test
business.industry
Pulmonary inflammation
lcsh:RM1-950
Elastase
cirrhose du foie
santé humaine
medicine.disease
3. Good health
[SDV] Life Sciences [q-bio]
[SDV.GEN.GA]Life Sciences [q-bio]/Genetics/Animal genetics
lcsh:Therapeutics. Pharmacology
030104 developmental biology
Endocrinology
medicine.anatomical_structure
biology.protein
inflammation pulmonaire
business
030217 neurology & neurosurgery
Zdroj: 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)
ISSN: 1663-9812
DOI: 10.3389/fphar.2018.00545
Popis: 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.
Databáze: OpenAIRE
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