ArticleImmunology2022
Itaconate and fumarate derivatives inhibit priming and activation of the canonical NLRP3 inflammasome in macrophages.
Article in Immunology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
43 citing papers in PubMed, 65 citations in OpenAlex.
- Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial.Nature communications · 2024Trial
- Itaconate: a dual-edged sword in immunometabolism and host-pathogen interactions.Archives of microbiology · 2026Review
- Itaconation and Succination as Metabolite-Derived Cysteine Modifications in Inflammatory Signalling: Biochemical Mechanisms, Chemoproteomic Mapping, and Therapeutic Opportunities.Cell biochemistry and biophysics · 2026Review
- NEK7 Cys298 is important for NLRP3 inflammasome and targetable by dimethyl fumarate.Cell chemical biology · 2026Article
- Caspase-1 in cancer and inflammatory diseases: a potential therapeutic target.Apoptosis : an international journal on programmed cell death · 2026Review
- Targeting the mitochondrial metabolite-dynamics-MDVs-MitoEVs axis: a new frontier in osteoarthritis management.Journal of translational medicine · 2026Review
- Mediterranean Pattern Diet in Multiple Sclerosis: A Review Focusing on Immunometabolites.Current neuropharmacology · 2026Review
- The KEAP1/NRF2 axis controls LPS-induced oxidative stress, inflammasome activation and caspase-1 activity in human endothelial cells.PloS one · 2026Article
- Macrophages dynamically integrate neuro-immune-microbial network signals: their role in gastrointestinal motility disorders and targeting potential.Frontiers in immunology · 2026Review
- Hepatic mitochondrial signaling as a systemic hub: inter-organ communication networks in aging and aging-related diseases.Frontiers in cell and developmental biology · 2026Review
- Immunomodulatory and anti-inflammatory potential of S-nitrosoglutathione (GSNO) in multiple sclerosis: a review of mechanisms and therapeutic perspectives.Frontiers in immunology · 2026Review
- Fumarate and fumarate hydratase: an immunometabolite regulator of inflammation and diseases.Frontiers in immunology · 2026Review
- The role of 25-hydroxycholesterol in the pathophysiology of brain vessel dysfunction associated with infection and cholesterol dysregulation.Disease models & mechanisms · 2025Article
- Itaconic Acid: A Regulator of Immune Responses and Inflammatory Metabolism.Current issues in molecular biology · 2025Review
- Targeting alveolar macrophages: a promising intervention for pulmonary infection and acute lung injury.Cellular & molecular biology letters · 2025Review
- Dimethyl Itaconate Alleviates Escherichia coli-Induced Endometritis Through the Guanosine-CXCL14 Axis via Increasing the Abundance of norank_f_Muribaculaceae.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- 4-octyl itaconate reduces human NLRP3 inflammasome constitutive activation with the cryopyrin-associated periodic syndrome p.R262W, p.D305N and p.T350M variants.Cellular and molecular life sciences : CMLS · 2025Article
- Time-of-day control of mitochondria regulates NLRP3 inflammasome activation in macrophages.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
- The role of the interplay between macrophage glycolytic reprogramming and NLRP3 inflammasome activation in acute lung injury/acute respiratory distress syndrome.Clinical and translational medicine · 2024Review
- Microglial Mayhem NLRP3 Inflammasome's Role in Multiple Sclerosis Pathology.CNS neuroscience & therapeutics · 2024Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
The NLRP3 inflammasome is a multiprotein complex that regulates caspase-1 activation and subsequent interleukin (IL)-1β and IL-18 release from innate immune cells in response to infection or injury. Derivatives of the metabolites itaconate and fumarate, dimethyl itaconate (DMI), 4-octyl itaconate (4OI) and dimethyl fumarate (DMF) limit both expression and release of IL-1β following NLRP3 inflammasome activation. However, the direct effects of these metabolite derivatives on NLRP3 inflammasome responses require further investigation. Using murine bone marrow-derived macrophages, mixed glia and organotypic hippocampal slice cultures (OHSCs), we demonstrate that DMI, 4OI and DMF pretreatments inhibit pro-inflammatory cytokine production in response to lipopolysaccharide (LPS), as well as inhibit subsequent NLRP3 inflammasome activation induced by nigericin. DMI, 4OI, DMF and monomethyl fumarate (MMF), another fumarate derivative, also directly inhibited biochemical markers of NLRP3 activation in LPS-primed macrophages, mixed glia, OHSCs and human macrophages in response to nigericin and imiquimod, including ASC speck formation, caspase-1 activation, gasdermin D cleavage and IL-1β release. DMF, an approved treatment of multiple sclerosis, as well as DMI, 4OI and MMF, inhibited NLRP3 activation in macrophages in response to lysophosphatidylcholine, which is used to induce demyelination, suggesting a possible mechanism for DMF in multiple sclerosis through NLRP3 inhibition. The derivatives also reduced pro-IL-1α cleavage in response to the calcium ionophore ionomycin. Together, these findings reveal the immunometabolic regulation of both the priming and activation steps of NLRP3 activation in macrophages. Furthermore, we highlight itaconate and fumarate derivatives as potential therapeutic options in NLRP3- and IL-1α-driven diseases, including in the brain.
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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.