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[[Inflammation and drug metabolism: NF-kappB and the CAR and PXR xeno-receptors].
- Source :
-
Medecine sciences : M/S [Med Sci (Paris)] 2008 Mar; Vol. 24 (3), pp. 301-5. - Publication Year :
- 2008
-
Abstract
- Decreased drug metabolism, hyperbilirubinemia and intrahepatic cholestasis are frequently observed during inflammation. Additionally, it has long been appreciated that exposure to drug metabolism-inducing xenobiotics can impair immune function. The nuclear receptor CAR (constitutive androstane receptor or NR1I3) and PXR (pregnane X receptor, NR1I2) control phase I (cytochrome P450 2B and 3A), phase II (GSTA, UGT1A1), and transporter (MDR1, SLC21A6, MRP2) genes involved in drugs metabolism, bile acids and bilirubin clearance in response to xenobiotics. It is well known that inflammation, through the activation of NF-kappaB pathway, leads to a decrease of CAR, PXR and RXRalpha expression and the expression of their target genes. In addition, a new study reveals the mutual repression between PXR and NF-kappaB signaling pathways, providing a molecular mechanism linking xenobiotic metabolism and inflammation.
- Subjects :
- Animals
Bile Acids and Salts metabolism
Bilirubin metabolism
Constitutive Androstane Receptor
Cytokines physiology
Gene Expression Regulation physiology
Glucocorticoids physiology
Humans
Hyperbilirubinemia etiology
Inactivation, Metabolic physiology
Infections immunology
Infections metabolism
Inflammation complications
Inflammation immunology
Inflammation physiopathology
Liver metabolism
Metabolic Clearance Rate
Mice
Mice, Knockout
Pregnane X Receptor
Signal Transduction physiology
Biotransformation physiology
Inflammation metabolism
NF-kappa B physiology
Receptors, Cytoplasmic and Nuclear physiology
Receptors, Steroid physiology
Transcription Factors physiology
Xenobiotics pharmacokinetics
Subjects
Details
- Language :
- French
- ISSN :
- 0767-0974
- Volume :
- 24
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Medecine sciences : M/S
- Publication Type :
- Academic Journal
- Accession number :
- 18334180
- Full Text :
- https://doi.org/10.1051/medsci/2008243301