ArticlePloS one2019
Pregnane X receptor activation constrains mucosal NF-κB activity in active inflammatory bowel disease.
Article in PloS one, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 30 citations in OpenAlex.
- Medications That Regulate Pregnane X Receptor: A Systematic Review of Current Evidence.Pharmacology research & perspectives · 2026Pooled it
- Pregnane X receptor (NR1I2) deficiency in mice reveals context-dependent regulation of inflammatory homeostasis.Frontiers in immunology · 2026Review
- Patchouli alcohol suppressesFrontiers in pharmacology · 2026Article
- Physiological Functions and Pathological Roles of PXR.Journal of the Endocrine Society · 2025Review
- Gut microbial metabolite indole-3-propionic acid inhibits inflammation and restores blood-milk barrier inFrontiers in microbiology · 2025Article
- Nuclear Receptors and Stress Response Pathways Associated with the Development of Oral Mucositis Induced by Antineoplastic Agents.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Review
- The epithelium takes the stage in asthma and inflammatory bowel diseases.Frontiers in cell and developmental biology · 2024Review
- Research Models to Mimic Necrotizing Enterocolitis and Inflammatory Bowel Diseases: Focus on Extracellular Vesicles Action.Stem cells (Dayton, Ohio) · 2023Review
- Protocatechuic acid inhibits LPS-induced mastitis in mice through activating the pregnane X receptor.Journal of cellular and molecular medicine · 2023Article
- Stem cell-derived intestinal organoids: a novel modality for IBD.Cell death discovery · 2023Review
- Bile acids and their receptors: Potential therapeutic targets in inflammatory bowel disease.World journal of gastroenterology · 2023Review
- Review
- Patient-derived organoids for therapy personalization in inflammatory bowel diseases.World journal of gastroenterology · 2022Review
- Gut mucosa dissociation protocols influence cell type proportions and single-cell gene expression levels.Scientific reports · 2022Article
- Article
- St. John's Wort alleviates dextran sodium sulfate-induced colitis through pregnane X receptor-dependent NFκB antagonism.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- Isotype-specific Antibody Responses to Mycobacterium avium paratuberculosis Antigens Are Associated With the Use of Biologic Therapy in Inflammatory Bowel Disease.Journal of Crohn's & colitis · 2021Article
- Oridonin Attenuates TNBS-induced Post-inflammatory Irritable Bowel Syndrome via PXR/NF-κB Signaling.Inflammation · 2021Article
- Deciphering structural bases of intestinal and hepatic selectivity in targeting pregnane X receptor with indole-based microbial mimics.Bioorganic chemistry · 2021Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe Pregnane X Receptor (PXR) is a principal signal transducer in mucosal responses to xenobiotic stress. It is well-recognized that inflammatory bowel disease is accompanied by xenobiotic stress, but the importance of the PXR in limiting inflammatory responses in inflammatory bowel disease remains obscure at best.
methodsWe stimulate a total of 106 colonic biopsies from 19 Crohn's disease patients with active disease, 36 colonic biopsies from 8 control patients, colonic organoids and various cell culture models (either proficient or genetically deficient with respect to PXR) in vitro with the PXR ligand rifampicin or vehicle. Effects on NF-κB activity are assessed by measuring interleukin-8 (IL-8) and interleukin-1ß (IL-1ß) mRNA levels by qPCR and in cell culture models by NF-κB reporter-driven luciferase activity and Western blot for signal transduction elements.
resultsWe observe a strict inverse correlation between colonic epithelial PXR levels and NF-κB target gene expression in colonic biopsies from Crohn's disease patients. PXR, activated by rifampicin, is rate-limiting for mucosal NF-κB activation in IBD. The correlation between colonic epithelial PXR levels and NF-κB target gene expression was also observed in intestinal organoids system. Furthermore, in preclinical in vitro models of intestinal inflammation, including intestinal organoids, genetic inactivation of PXR unleashes NF-κB-dependent signal transduction whereas conversely NF-κB signaling reduces levels of PXR expression.
conclusionsOur data indicate that the PXR is a major and clinically relevant antagonist of NF-κB activity in the intestinal epithelial compartment during inflammatory bowel disease.
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Registered trials
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