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Interleukin-6 negatively regulates the expression of pregnane X receptor and constitutively activated receptor in primary human hepatocytes.

Abstract：

:The marked impairment of hepatic drug metabolism during inflammation and infections has been known for many years and shown to result from down-regulation of cytochrome P450s (CYP) by cytokines. However, the mechanism of this repression is unknown. Using primary cultures of human hepatocytes, we show here that interleukin-6 (IL-6) rapidly and markedly decreases the expression of PXR (pregnane X receptor) and CAR (constitutively activated receptor) mRNAs, but does not affect the levels of dioxin receptor and glucocorticoid receptor mRNA. In parallel, IL-6 decreases both rifampicin- and phenobarbital-mediated induction of CYP2B6, CYP2C8, CYP2C9, and CYP3A4. As the transcriptional activity of PXR and CAR is not affected by IL-6 in cell-based reporter assays, our data suggest that the loss of CYP2 and CYP3 inducibility results from the negative regulation of PXR and CAR gene expression by this cytokine.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Pascussi JM,Gerbal-Chaloin S,Pichard-Garcia L,Daujat M,Fabre JM,Maurel P,Vilarem MJ

doi

10.1006/bbrc.2000.3219

subject

Has Abstract

pub_date

2000-08-11 00:00:00

pages

707-13

issue

3

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(00)93219-4

journal_volume

274

pub_type

杂志文章

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