细胞因子对细胞色素P450的抑制作用：白细胞介素-1β可抵消氯贝酸对培养的胎鼠肝细胞中CYP4A的诱导作用。

Repression of cytochrome P450 by cytokines: IL-1 beta counteracts clofibric acid induction of CYP4A in cultured fetal rat hepatocytes.

作者信息

Parmentier J H, Kremers P, Ferrari L, Batt A M, Gielen J E, Siest G

机构信息

Centre du Médicament, URA CNRS 597, Université de Nancy I, France.

出版信息

Cell Biol Toxicol. 1993 Jul-Sep;9(3):307-13. doi: 10.1007/BF00755608.

DOI:10.1007/BF00755608

PMID:8299008

Abstract

Interleukin-1 is known to repress a number of hepatic drug-metabolizing enzymes in rats and humans. The effect of interleukin-1 beta on lauric acid 12-hydroxylase (CYP4A family) was studied in cultured fetal rat hepatocytes after clofibric acid induction. Dexamethasone was used as an agent promoting differentiation and long-term maintenance of active hepatocytes. Dexamethasone and clofibric acid in combination allowed maximal (13.5-fold) induction of CYP4A1. Lauric acid 12-hydroxylase activity was found to increase with time in culture. Interleukin-1 beta adversely affected P4504A clofibric acid-induced activity, totally eliminating the effect of induction at doses exceeding 5 ng/ml. This repression/inhibition was dose-dependent. The mechanism by which interleukin-1 beta prevents the development of cytochrome P4504A activity is unclear.

摘要

已知白细胞介素-1可抑制大鼠和人类体内的多种肝脏药物代谢酶。在经氯贝酸诱导的培养胎鼠肝细胞中，研究了白细胞介素-1β对月桂酸12-羟化酶（CYP4A家族）的影响。地塞米松用作促进活性肝细胞分化和长期维持的试剂。地塞米松和氯贝酸联合使用可使CYP4A1的诱导作用达到最大（13.5倍）。发现月桂酸12-羟化酶活性随培养时间增加。白细胞介素-1β对氯贝酸诱导的P4504A活性产生不利影响，在剂量超过5 ng/ml时完全消除诱导作用。这种抑制作用呈剂量依赖性。白细胞介素-1β阻止细胞色素P4504A活性发展的机制尚不清楚。