Regulation of CYP4A1 and peroxisome proliferator-activated receptor alpha expression by interleukin-1beta, interleukin-6, and dexamethasone in cultured fetal rat hepatocytes.
Biochem Pharmacol
; 54(8): 889-98, 1997 Oct 15.
Article
in En
| MEDLINE
| ID: mdl-9354589
ABSTRACT
The CYP4A1 isoenzyme induced in rodents by peroxisome proliferators is known to be repressed at a pretranslational level by interferon. Interleukin-1beta (IL-1beta) also reduces CYP4A1-related 12-laurate hydroxylase activity in cultured fetal rat hepatocytes after induction by clofibric acid. In this fetal hepatocyte model, IL-1beta and interleukin-6 (IL-6) were tested for their ability to reduce 12-laurate hydroxylase activity, CYP4A1 apoprotein content, and the CYP4A1 mRNA level. IL-1beta and IL-6 strongly diminished CYP4A1 activity and apoprotein and mRNA levels in a dose- and time-dependent manner. CYP4A1 expression is thus down-regulated at a pretranslational level by these cytokines. As it has been shown that the peroxisome proliferator-activated receptor alpha (PPAR alpha) mediates the induction of the CYP4A1 gene by a peroxisome proliferator, the capacity of IL-1beta or IL-6 to modulate the PPAR alpha mRNA level was tested. It was found that IL-1beta and IL-6 both repress the induction of PPAR alpha expression exerted by the combined action of clofibric acid and dexamethasone. However, even at the highest concentration (10 ng/mL) tested for both cytokines, IL-1beta as well as IL-6 failed to abolish the induction of CYP4A1 by dexamethasone. The mechanism of the protective effect of the synthetic glucocorticoid on CYP4A1 repression by interleukins is discussed.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Transcription Factors
/
Dexamethasone
/
Interleukin-6
/
Interleukin-1
/
Receptors, Cytoplasmic and Nuclear
/
Cytochrome P-450 Enzyme System
/
Mixed Function Oxygenases
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Biochem Pharmacol
Year:
1997
Document type:
Article
Affiliation country:
Belgium
Publication country:
ENGLAND
/
ESCOCIA
/
GB
/
GREAT BRITAIN
/
INGLATERRA
/
REINO UNIDO
/
SCOTLAND
/
UK
/
UNITED KINGDOM