ArticleDrug metabolism and disposition: the biological fate of chemicals2014
Role of constitutive androstane receptor in Toll-like receptor-mediated regulation of gene expression of hepatic drug-metabolizing enzymes and transporters.
Article in Drug metabolism and disposition: the biological fate of chemicals, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 34 citations in OpenAlex.
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- Causative Role of Anoxic Environment in Bacterial Regulation of Human Intestinal Function.Cellular and molecular bioengineering · 2022Article
- Immunization and Drug Metabolizing Enzymes: Focus on Hepatic Cytochrome P450 3A.Expert review of vaccines · 2021Article
- Involvement of cytochrome P450 enzymes in inflammation and cancer: a review.Cancer chemotherapy and pharmacology · 2021Review
- Potential role of drug metabolizing enzymes in chemotherapy-induced gastrointestinal toxicity and hepatotoxicity.Expert opinion on drug metabolism & toxicology · 2020Review
- A non-lethal malarial infection results in reduced drug metabolizing enzyme expression and drug clearance in mice.Malaria journal · 2019Article
- Transcriptomic profiling identifies novel mechanisms of transcriptional regulation of the cytochrome P450 (Cyp)3a11 gene.Scientific reports · 2019Article
- Constitutive androstane receptor 1 is constitutively bound to chromatin and 'primed' for transactivation in hepatocytes.Molecular pharmacology · 2019Article
- Regulation of human placental drug transporters in HCV infection and their influence on direct acting antiviral medications.Placenta · 2018Article
- Role of c-Jun-N-Terminal Kinase in Pregnane X Receptor-Mediated Induction of Human Cytochrome P4503A4 In Vitro.Drug metabolism and disposition: the biological fate of chemicals · 2018Article
- Activation of Constitutive Androstane Receptor Ameliorates Renal Ischemia-Reperfusion-Induced Kidney and Liver Injury.Molecular pharmacology · 2018Article
- Hepatic Cyp1a2 Expression Reduction during Inflammation Elicited in a Rat Model of Intermittent Hypoxia.Chinese medical journal · 2017Article
- Role of Toll-like receptor 4 in drug-drug interaction between paclitaxel and irinotecan in vitro.Toxicology in vitro : an international journal published in association with BIBRA · 2017Article
- Characterizing drug-metabolizing enzymes and transporters that areActa pharmaceutica Sinica. B · 2016Article
- Regulation of PXR and CAR by protein-protein interaction and signaling crosstalk.Expert opinion on drug metabolism & toxicology · 2016Review
- Integrin Receptors Play a Key Role in the Regulation of Hepatic CYP3A.Drug metabolism and disposition: the biological fate of chemicals · 2016Article
- Role of Adaptor Protein Toll-Like Interleukin Domain Containing Adaptor Inducing Interferon β in Toll-Like Receptor 3- and 4-Mediated Regulation of Hepatic Drug Metabolizing Enzyme and Transporter Genes.Drug metabolism and disposition: the biological fate of chemicals · 2016Article
- Recql5 protects against lipopolysaccharide/D-galactosamine-induced liver injury in mice.World journal of gastroenterology · 2015Article
- Inflammatory stress increases hepatic CD36 translational efficiency via activation of the mTOR signalling pathway.PloS one · 2014Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Impairment of drug disposition in the liver during inflammation has been attributed to downregulation of gene expression of drug-metabolizing enzymes (DMEs) and drug transporters. Inflammatory responses in the liver are primarily mediated by Toll-like receptors (TLRs). We have recently shown that activation of TLR2 or TLR4 by lipoteichoic acid (LTA) and lipopolysaccharide (LPS), respectively, leads to the downregulation of gene expression of DMEs/transporters. However, the molecular mechanism underlying this downregulation is not fully understood. The xenobiotic nuclear receptors, pregnane X receptor (PXR) and constitutive androstane receptor (CAR), regulate the expression of DMEs/transporter genes. Downregulation of DMEs/transporters by LTA or LPS was associated with reduced expression of PXR and CAR genes. To determine the role of CAR, we injected CAR(+/+) and CAR(-/-) mice with LTA or LPS, which significantly downregulated (~40%-60%) RNA levels of the DMEs, cytochrome P450 (Cyp)3a11, Cyp2a4, Cyp2b10, uridine diphosphate glucuronosyltransferase 1a1, amine N-sulfotransferase, and the transporter, multidrug resistance-associated protein 2, in CAR(+/+) mice. Suppression of most of these genes was attenuated in LTA-treated CAR(-/-) mice. In contrast, LPS-mediated downregulation of these genes was not attenuated in CAR(-/-) mice. Induction of these genes by mouse CAR activator 1,4-bis-[2-(3,5-dichloropyridyloxy)]benzene was sustained in LTA- but not in LPS-treated mice. Similar observations were obtained in humanized CAR mice. We have replicated these results in primary hepatocytes as well. Thus, LPS can downregulate DME/transporter genes in the absence of CAR, whereas the effect of LTA on these genes is attenuated in the absence of CAR, indicating the potential involvement of CAR in LTA-mediated downregulation of DME/transporter genes.
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