EA 4427 Signalisation et Réponse aux Agents Infectieux et Chimiques, Institut de Recherches en Santé Environnement Travail, Université de Rennes 1, Rennes, France.
Fundam Clin Pharmacol. 2011 Feb;25(1):99-103. doi: 10.1111/j.1472-8206.2010.00822.x.
Interferon (IFN)-γ is known to downregulate expression of drug detoxifying proteins such as cytochromes P-450 (CYPs) in human hepatocytes. The present study was designed to determine whether IFN-γ may also impair expression of influx and efflux drug transporters, which constitute important determinants of the liver detoxification pathway. Exposure of primary human hepatocytes to 10 ng/mL IFN-γ was found to downregulate mRNA levels of sinusoidal influx transporters such as sodium-taurocholate cotransporting polypeptide, organic anion transporting polypeptide (OATP) 2B1, OATP1B1, and OATP1B3. IFN-γ concomitantly reduced mRNA expression of drug efflux pumps such as multidrug resistance gene 1, multidrug resistance protein (MRP) 2, MRP3, breast cancer resistance protein and bile salt export pump. Such IFN-γ-mediated repression of major hepatic drug transporters may contribute to impaired liver clearance of drugs administrated to patients suffering from inflammation or viral infections associated with increased secretion of IFN-γ.
干扰素 (IFN)-γ 已知可下调人肝细胞中药物解毒蛋白（如细胞色素 P-450（CYPs））的表达。本研究旨在确定 IFN-γ 是否也会损害流入和流出药物转运体的表达，这些转运体构成肝脏解毒途径的重要决定因素。研究发现，将原代人肝细胞暴露于 10ng/mL IFN-γ 可下调胆汁酸共转运多肽、有机阴离子转运多肽 (OATP) 2B1、OATP1B1 和 OATP1B3 等窦状隙流入转运体的 mRNA 水平。IFN-γ 同时降低了多药耐药基因 1、多药耐药蛋白 (MRP) 2、MRP3、乳腺癌耐药蛋白和胆盐输出泵等药物外排泵的 mRNA 表达。IFN-γ 介导的主要肝药物转运体的这种抑制作用可能导致与 IFN-γ 分泌增加相关的炎症或病毒感染患者所给予的药物肝脏清除率受损。
