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
INSERM, Centre de Recherche Saint-Antoine, Sorbonne Université, Paris, France.
Pediatric Respiratory Department, Trousseau Hospital, Assistance Publique - Hôpitaux de Paris, Paris, France.
Front Pharmacol. 2018 Jun 5;9:545. doi: 10.3389/fphar.2018.00545. eCollection 2018.
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-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.
囊性纤维化（CF）的特征是慢性肺部炎症。在CF中，糖皮质激素（GC）被广泛使用，但其疗效和效益/风险比仍存在争议。在血浆中，皮质类固醇结合球蛋白（CBG）结合90%的GC并将其输送到炎症部位。这项工作的主要目标是研究CF患者中CBG的表达，以确定CBG是否可用于优化GC治疗。通过qPCR和蛋白质印迹法在CF肝硬化患者和非CF肝硬化患者的肝脏样本中以及通过qPCR在非CF和CF患者的肺样本中测量CBG的表达。使用血浆进行与H-皮质醇的CBG结合试验以及弹性蛋白酶/α1-抗胰蛋白酶复合物的测量。CF患者肝脏中CBG在转录水平和蛋白质水平均增加，但血浆中未增加。这可能是由于血浆弹性蛋白酶增加所致。我们证明肺CBG在支气管和细支气管中表达，并且在CF肺中其表达在两个研究水平上均降低。尽管CF患者肝脏和肺中CBG的表达相反，但血浆中CBG的浓度正常。因此，在CF的情况下，例如在肺中，CBG可能有助于将对CBG具有高亲和力的优化合成GC输送到主要炎症部位。
