Literature DB >> 18334180

[[Inflammation and drug metabolism: NF-kappB and the CAR and PXR xeno-receptors].

Jean-Marc Pascussi1, Marie-José Vilarem.   

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.

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Year:  2008        PMID: 18334180     DOI: 10.1051/medsci/2008243301

Source DB:  PubMed          Journal:  Med Sci (Paris)        ISSN: 0767-0974            Impact factor:   0.818


  4 in total

Review 1.  Regulation of drug-metabolizing enzymes by xenobiotic receptors: PXR and CAR.

Authors:  Antonia H Tolson; Hongbing Wang
Journal:  Adv Drug Deliv Rev       Date:  2010-08-17       Impact factor: 15.470

2.  Transcriptional profiling suggests that Nevirapine and Ritonavir cause drug induced liver injury through distinct mechanisms in primary human hepatocytes.

Authors:  Ylva Terelius; Robert A Figler; Svetlana Marukian; Maria S Collado; Mark J Lawson; Aaron J Mackey; David Manka; Charles W Qualls; Brett R Blackman; Brian R Wamhoff; Ajit Dash
Journal:  Chem Biol Interact       Date:  2015-12-02       Impact factor: 5.192

3.  The novel antibacterial compound walrycin A induces human PXR transcriptional activity.

Authors:  Alexandre Berthier; Frédérik Oger; Céline Gheeraert; Abdel Boulahtouf; Rémy Le Guével; Patrick Balaguer; Bart Staels; Gilles Salbert; Philippe Lefebvre
Journal:  Toxicol Sci       Date:  2012-02-07       Impact factor: 4.109

4.  Expression, localization and polymorphisms of the nuclear receptor PXR in Barrett's esophagus and esophageal adenocarcinoma.

Authors:  Anouk van de Winkel; Vivianda Menke; Astrid Capello; Leon M G Moons; Raymond G J Pot; Herman van Dekken; Peter D Siersema; Johannes G Kusters; Luc J W van der Laan; Ernst J Kuipers
Journal:  BMC Gastroenterol       Date:  2011-10-06       Impact factor: 3.067

  4 in total

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