Opposite Expression of Hepatic and Pulmonary Corticosteroid-Binding Globulin in Cystic Fibrosis Patients
Front. Pharmacol.. 2018-06-05; 9:
Lire sur PubMed
1. Front Pharmacol. 2018 Jun 5;9:545. doi: 10.3389/fphar.2018.00545. eCollection
Opposite Expression of Hepatic and Pulmonary Corticosteroid-Binding Globulin in
Cystic Fibrosis Patients.
Tchoukaev A(1), Taytard J(1)(2), Rousselet N(1), Rebeyrol C(1), Debray D(1)(3),
Blouquit-Laye S(4), Moisan MP(5), Foury A(5), Guillot L(1), Corvol H(1)(2),
Tabary O(1), Le Rouzic P(1).
(1)INSERM, Centre de Recherche Saint-Antoine, Sorbonne Université, Paris, France.
(2)Pediatric Respiratory Department, Trousseau Hospital, Assistance Publique –
Hôpitaux de Paris, Paris, France.
(3)Pediatric Hepatology Unit, Necker Enfants Malades Hospital, Paris, France.
(4)INSERM U1173, UFR des Sciences de la Santé Simone Veil, Université de
Versailles Saint-Quentin-en-Yvelines, Versailles, France.
(5)INRA, Laboratoire NutriNeurO, UMR 1286, Université de Bordeaux, Bordeaux,
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.,