ArticleProceedings of the National Academy of Sciences of the United States of America2017
Uric acid priming in human monocytes is driven by the AKT-PRAS40 autophagy pathway.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 95 papers.
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Who cites it
95 citing papers in PubMed, 154 citations in OpenAlex.
- Effective xanthine oxidase inhibitor urate lowering therapy in gout is linked to an emergent serum protein interactome of complement and inflammation modulators.Scientific reports · 2024Trial
- Beyond the Prevention of Anti-drug Antibody Formation with Uricase Therapy: Mechanistic Roles of DMARDs in Modifying Gout Flare Risk.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026Review
- Soluble uric acid enhances gouty inflammation via activating gene expression related to innate immune responses, M1 macrophage polarization and urate crystal phagocytosis in mouse macrophage-like cells: novel insights into its mechanisms from RNA sequencing.Hypertension research : official journal of the Japanese Society of Hypertension · 2026Article
- Pharmacological inhibition of PGK1 suppresses EGFR-positive esophageal squamous cell carcinoma by dual targeting of glycolysis and autophagy-dependent EGFR degradation.Cellular oncology (Dordrecht, Netherlands) · 2026Article
- Treat-to-Target Urate-lowering Therapy: Lessons Learned from the STOP Gout Study.Current rheumatology reports · 2026Review
- Article
- Pentagalloyl glucose Suppresses MSU Crystal-Induced Gout Inflammation and Arachidonic Acid Production In Vitro and In Vivo.Research square · 2026Article
- Review
- Priming of human monocytes by β-glucan and obesity-associated factors: modifications to global DNA methylation, gene expression, phenotype and function.Frontiers in immunology · 2026Article
- Immunometabolic regulation in gouty arthritis: current evidence, mechanistic insights, and remaining challenges.Frontiers in immunology · 2026Review
- Bibliometric and Visual Analysis of Trained Immunity from 2005 to 2024.Journal of inflammation research · 2026Review
- Dual role of autophagy in gouty arthritis (GA): molecular mechanisms and therapeutic potential.Frontiers in immunology · 2026Review
- Pentagalloyl glucose suppresses MSU crystal-induced gout inflammation and arachidonic acid productionFrontiers in pharmacology · 2026Article
- Trained Immunity and Cardiovascular Risk: An Immunological Perspective.Immunological reviews · 2026Review
- Gut microbiota: a potential therapeutic target for hyperuricemia and gout.Bioscience of microbiota, food and health · 2026Review
- Trained immunity in chronic rhinosinusitis: epigenetic reprogramming of innate immune memory as a driver of mucosal inflammation and recurrence.Frontiers in immunology · 2026Review
- Risk factors and a nomogram for predicting severe acute kidney injury in pediatric sepsis: a retrospective study.Frontiers in pediatrics · 2026Article
- Therapeutic potential of traditional Chinese medicine for hyperuricemia: mechanistic insights and clinical prospects.Frontiers in pharmacology · 2026Review
- Examining the Interaction between Allergic Asthma and Air Pollution: a Potential Role for Trained Immunity.Current allergy and asthma reports · 2025Review
- Cross-sectional mediation analysis of systemic inflammation in the association between serum uric acid and diabetic kidney disease: Evidence from NHANES 1999-2018.Metabolism open · 2025Article
35 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 4 institutions in 3 countries.
Funding
Abstract
Metabolic triggers are important inducers of the inflammatory processes in gout. Whereas the high serum urate levels observed in patients with gout predispose them to the formation of monosodium urate (MSU) crystals, soluble urate also primes for inflammatory signals in cells responding to gout-related stimuli, but also in other common metabolic diseases. In this study, we investigated the mechanisms through which uric acid selectively lowers human blood monocyte production of the natural inhibitor IL-1 receptor antagonist (IL-1Ra) and shifts production toward the highly inflammatory IL-1β. Monocytes from healthy volunteers were first primed with uric acid for 24 h and then subjected to stimulation with lipopolysaccharide (LPS) in the presence or absence of MSU. Transcriptomic analysis revealed broad inflammatory pathways associated with uric acid priming, with NF-κB and mammalian target of rapamycin (mTOR) signaling strongly increased. Functional validation did not identify NF-κB or AMP-activated protein kinase phosphorylation, but uric acid priming induced phosphorylation of AKT and proline-rich AKT substrate 40 kDa (PRAS 40), which in turn activated mTOR. Subsequently, Western blot for the autophagic structure LC3-I and LC3-II (microtubule-associated protein 1A/1B-light chain 3) fractions, as well as fluorescence microscopy of LC3-GFP-overexpressing HeLa cells, revealed lower autophagic activity in cells exposed to uric acid compared with control conditions. Interestingly, reactive oxygen species production was diminished by uric acid priming. Thus, the Akt-PRAS40 pathway is activated by uric acid, which inhibits autophagy and recapitulates the uric acid-induced proinflammatory cytokine phenotype.
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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.