ArticleAmerican journal of physiology. Gastrointestinal and liver physiology2014
Activation of N-methyl-d-aspartate receptor downregulates inflammasome activity and liver inflammation via a β-arrestin-2 pathway.
Article in American journal of physiology. Gastrointestinal and liver physiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
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Who cites it
20 citing papers in PubMed, 27 citations in OpenAlex.
- GPCRs as key regulators in wound healing.Frontiers in cell and developmental biology · 2026Review
- Synthesis and Anti-Liver Fibrosis Research of Aspartic Acid Derivatives.Molecules (Basel, Switzerland) · 2024Article
- Constituents fromMolecules (Basel, Switzerland) · 2024Article
- Review
- The Efficacy of Intratissue Percutaneous Electrolysis (EPIInternational journal of molecular sciences · 2024Article
- Aspartate Reduces Liver Inflammation and Fibrosis by Suppressing the NLRP3 Inflammasome Pathway via Upregulating NS3TP1 Expression.Journal of personalized medicine · 2023Article
- Review
- Kynurenic Acid Acts as a Signaling Molecule Regulating Energy Expenditure and Is Closely Associated With Metabolic Diseases.Frontiers in endocrinology · 2022Review
- Identification of Lactate as a Cardiac Protectant by Inhibiting Inflammation and Cardiac Hypertrophy Using a Zebrafish Acute Heart Failure Model.Pharmaceuticals (Basel, Switzerland) · 2021Article
- Pathophysiologic Role of Neurotransmitters in Digestive Diseases.Frontiers in physiology · 2021Review
- Aspartate Metabolism Facilitates IL-1β Production in Inflammatory Macrophages.Frontiers in immunology · 2021Article
- Higher CSF Levels of NLRP3 Inflammasome Is Associated With Poor Prognosis of Anti-N-methyl-D-Aspartate Receptor Encephalitis.Frontiers in immunology · 2019Article
- Ketamine induces hippocampal apoptosis through a mechanism associated with the caspase-1 dependent pyroptosis.Neuropharmacology · 2018Article
- A NMDA-receptor calcium influx assay sensitive to stimulation by glutamate and glycine/D-serine.Scientific reports · 2017Article
- Key Events Participating in the Pathogenesis of Alcoholic Liver Disease.Biomolecules · 2017Review
- Sepsis-induced selective loss of NMDA receptors modulates hippocampal neuropathology in surviving septic mice.PloS one · 2017Article
- A novel "complement-metabolism-inflammasome axis" as a key regulator of immune cell effector function.European journal of immunology · 2016Review
- Non-alcoholic steatohepatitis: emerging molecular targets and therapeutic strategies.Nature reviews. Drug discovery · 2016Review
- Multifaceted role of β-arrestins in inflammation and disease.Genes and immunity · 2015Review
- Inflammasomes in pancreatic physiology and disease.American journal of physiology. Gastrointestinal and liver physiology · 2015Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Activation of the cytosolic inflammasome machinery is responsible for acute and chronic liver inflammation, but little is known about its regulation. The N-methyl-d-aspartate (NMDA) receptor families are heterotetrameric ligand-gated ion channels that are activated by a range of metabolites, including aspartate, glutamate, and polyunsaturated fatty acids. In the brain NMDA receptors are present on neuronal and nonneuronal cells and regulate a diverse range of functions. We tested the role of the NMDA receptor and aspartate in inflammasome regulation in vitro and in models of acute hepatitis and pancreatitis. We demonstrate that the NMDA receptor is present on Kupffer cells, and their activation on primary mouse and human cells limits inflammasome activation by downregulating NOD-like receptor family, pyrin domain containing 3 and procaspase-1. The NMDA receptor pathway is active in vivo, limits injury in acute hepatitis, and can be therapeutically further activated by aspartate providing protection in acute inflammatory liver injury. Downregulation of inflammasome activation by NMDA occurs via a β-arrestin-2 NF-kβ and JNK pathway and not via Ca(2+) mobilization. We have identified the NMDA receptor as a regulator of inflammasome activity in vitro and in vivo. This has identified a new area of immune regulation associated by metabolites that may be relevant in a diverse range of conditions, including nonalcoholic steatohepatitis and total parenteral nutrition-induced immune suppression.
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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.