REPRESSION OF CYTOCHROME-P450 BY CYTOKINES - IL-1-BETA COUNTERACTS CLOFIBRIC ACID INDUCTION OF CYP4A IN CULTURED FETAL-RAT HEPATOCYTES

被引：20

作者：

PARMENTIER, JH

KREMERS, P

FERRARI, L

BATT, AM

GIELEN, JE

SIEST, G

机构：

[1] UNIV LIEGE, CHIM MED LAB, B-4000 LIEGE, BELGIUM

[2] UNIV NANCY 1, CTR MED, CNRS, URA 597, F-54000 NANCY, FRANCE

来源：

CELL BIOLOGY AND TOXICOLOGY | 1993年 / 9卷 / 03期

关键词：

CLOFIBRIC ACID; CYTOCHROME P450; HEPATOCYTE; INTERLEUKIN-1; LAURIC ACID;

D O I：

10.1007/BF00755608

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页码：307 / 313

页数：7

共 23 条

[1]

BARKER CW, 1992, J BIOL CHEM, V267, P8050

[2] LONG-TERM MAINTENANCE OF MONOXYGENASE ACTIVITIES IN CULTURED FETAL-RAT HEPATOCYTES [J].

BOLLINNE, A ;

KREMERS, P ;

KOLODZICI, C ;

GIELEN, JE .

CELL DIFFERENTIATION, 1987, 21 (04) :239-246

[3] MECHANISM-BASED PROBES OF THE TOPOLOGY AND FUNCTION OF FATTY-ACID HYDROXYLASES [J].

DEMONTELLANO, PRO ;

CHAN, WK ;

TUCK, SF ;

KAIKAUS, RM ;

BASS, NM ;

PETERSON, JA .

FASEB JOURNAL, 1992, 6 (02) :695-699

[4]

DIGIOVINE FS, 1990, IMMUNOL TODAY, V11, P13

[5]

DINARELLO CA, 1992, INTERLEUKINS MOL BIO, V51, P1

[6]

DOWER SK, 1992, CHEM IMMUNOL, V51, P33

[7]

FERRARI L, 1992, DRUG METAB DISPOS, V20, P407

[8] ROLE OF INTERLEUKIN-1 IN THE DEPRESSION OF LIVER DRUG-METABOLISM BY ENDOTOXIN [J].

GHEZZI, P ;

SACCARDO, B ;

VILLA, P ;

ROSSI, V ;

BIANCHI, M ;

DINARELLO, CA .

INFECTION AND IMMUNITY, 1986, 54 (03) :837-840

[9]

GIBSON GG, 1991, METHOD ENZYMOL, V206, P353

[10]

ISSEMANN I, 1990, NATURE, V347, P645, DOI 10.1038/347645a0

← 1 2 3 →