ArticleToxicological sciences : an official journal of the Society of Toxicology2010
Kynurenic acid is a potent endogenous aryl hydrocarbon receptor ligand that synergistically induces interleukin-6 in the presence of inflammatory signaling.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 384 papers.
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Who cites it
384 citing papers in PubMed, 622 citations in OpenAlex.
- Exercise Diminishes Plasma Neurofilament Light Chain and Reroutes the Kynurenine Pathway in Multiple Sclerosis.Neurology(R) neuroimmunology & neuroinflammation · 2021Trial
- Acute exercise impacts AhR and PD-1 levels of CD8European journal of applied physiology · 2021Trial
- Gut microbiota and metabolic characteristics in PWHIV with metabolic dysfunction-associated steatotic liver disease (MASLD).Virulence · 2027Article
- Tryptophan metabolism in colorectal cancer: From mechanistic insights to novel therapeutic strategies.Clinical and translational medicine · 2026Review
- The Kynurenine Pathway in Tuberculosis: Focus on Immunometabolic Regulation, Compartment-Specific Biology, and Therapeutic Potential.Life (Basel, Switzerland) · 2026Review
- Tryptophan Metabolism and Aryl-Hydrocarbon Receptor Agonists in the Gut Microbiome of People With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.MicrobiologyOpen · 2026Article
- Nanoparticles isolated from the Gubi Zhitong formula alleviate knee osteoarthritis by reprogramming macrophages.Materials today. Bio · 2026Article
- Tryptophan Metabolism at the Crossroads of Immunity, Barrier Function, and the Microbiome in Atopic Dermatitis.Clinical reviews in allergy & immunology · 2026Review
- The Tryptophan Paradox: From Microbiome-Mediated Homeostasis to Tumor-Driven Immune Escape.International journal of molecular sciences · 2026Review
- Cell Signaling by Tryptophan Catabolism.Biochemistry · 2026Review
- Fasting and Caloric Restriction Activate an ADIOL-NHR-91-Kynurenine Pathway Signaling Axis to Promote Healthspan.Aging cell · 2026Article
- Stage-Dependent Changes in Kynurenine Pathway Enzyme Expression Suggest Immune-Related Involvement in Bladder Cancer Progression.International journal of urology : official journal of the Japanese Urological Association · 2026Article
- Artemether and Euphorbia factor L9 suppress kynurenine production through distinct effects on tryptophan metabolism.The Biochemical journal · 2026Article
- Tryptophan metabolites 3-hydroxykynurenine (3HK) and 3-hydroxyanthranilic acid (3HAA) increase oxidative stress and impair osteoblastic bone formation.The Journal of biological chemistry · 2026Article
- Kynurenine pathway dysregulation in major depressive disorder: the convergence of excitotoxicity, neuroinflammation, and oxidative stress.Journal of neuroinflammation · 2026Review
- Circadian tryptophan metabolism contributes to systemic aryl hydrocarbon receptor activity.iScience · 2026Article
- Metformin and Sitagliptin Impact the Brain Kynurenine Pathway: Region-Specific Modulation of Neuroactive Metabolites in Non-Diabetic Male Rats.Molecules (Basel, Switzerland) · 2026Article
- Receptor-Mitochondria Crosstalk in the Kynurenine Metabolic Pathway: Integrating Metabolomics and Clinical Mass Spectrometry.Antioxidants (Basel, Switzerland) · 2026Review
- Dynamics of tryptophan metabolites and microbial adaptations during corn by-product fermentation in the pig gut microbiome.Journal of animal science and biotechnology · 2026Article
- Metabolic Mechanisms in Electroconvulsive Therapy for Schizophrenia: Role, Potential and Future Directions.International journal of molecular sciences · 2026Review
324 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Inflammatory signaling plays a key role in tumor progression, and the pleiotropic cytokine interleukin-6 (IL-6) is an important mediator of protumorigenic properties. Activation of the aryl hydrocarbon receptor (AHR) with exogenous ligands coupled with inflammatory signals can lead to synergistic induction of IL6 expression in tumor cells. Whether there are endogenous AHR ligands that can mediate IL6 production remains to be established. The indoleamine-2,3-dioxygenase pathway is a tryptophan oxidation pathway that is involved in controlling immune tolerance, which also aids in tumor escape. We screened the metabolites of this pathway for their ability to activate the AHR; results revealed that kynurenic acid (KA) is an efficient agonist for the human AHR. Structure-activity studies further indicate that the carboxylic acid group is required for significant agonist activity. KA is capable of inducing CYP1A1 messenger RNA levels in HepG2 cells and inducing CYP1A-mediated metabolism in primary human hepatocytes. In a human dioxin response element-driven stable reporter cell line, the EC(25) was observed to be 104nM, while in a mouse stable reporter cell line, the EC(25) was 10muM. AHR ligand competition binding assays revealed that KA is a ligand for the AHR. Treatment of MCF-7 cells with interleukin-1beta and a physiologically relevant concentration of KA (e.g., 100nM) leads to induction of IL6 expression that is largely dependent on AHR expression. Our findings have established that KA is a potent AHR endogenous ligand that can induce IL6 production and xenobiotic metabolism in cells at physiologically relevant concentrations.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.