ArticleJournal of inflammation (London, England)2024
Resolution of acute inflammation induced by monosodium urate crystals (MSU) through neutrophil extracellular trap-MSU aggregate-mediated negative signaling.
Article in Journal of inflammation (London, England), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.
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Who cites it
10 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Ferroptosis in gouty arthritis: a potential therapeutic strategy.Frontiers in immunology · 2026Pooled it
- Uric Acid as a Redox Switch in Gout: Linking Xanthine Oxidoreductase-Derived ROS, NLRP3 Inflammasome Activation and Emerging Ferroptotic Mechanisms.Antioxidants (Basel, Switzerland) · 2026Review
- Exploratory study of DEFB1 genetic variants and human β-defensin-1 expression in monosodium urate crystal-induced arthritis: insights into innate immune regulation.Molecular biology reports · 2026Article
- Pentagalloyl glucose Suppresses MSU Crystal-Induced Gout Inflammation and Arachidonic Acid Production In Vitro and In Vivo.Research square · 2026Article
- Spatiotemporal immune gradients in gout: immune response-driven activation of the NLRP3-IL-1β axis and its transition to trained immunity.Frontiers in immunology · 2026Review
- Pentagalloyl glucose suppresses MSU crystal-induced gout inflammation and arachidonic acid productionFrontiers in pharmacology · 2026Article
- Antiarthritic activities of berberine in a rat model of gouty arthritis.Scientific reports · 2025Article
- NETs: a new target for autoimmune disease.Frontiers in immunology · 2025Review
- Modulation of IRAK4 as a therapeutic strategy against monosodium urate- and xanthine-induced inflammation in macrophages and HepG2 cells.Frontiers in immunology · 2025Article
- From genetic causality to druggable targets: A multiomics framework identifies ZSCAN16 in gout pathogenesis.Science progressArticle
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8 authors.
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Abstract
backgroundPolymorphonuclear neutrophils (PMN) activation by monosodium urate crystals (MSU) is crucial to acute gouty arthritis and subsequent spontaneous remission within 7-10 days. Activated PMNs release neutrophil extracellular traps (NETs) that entrap MSU crystals, forming NET-MSU aggregates. Whether NET-MSU aggregates contribute to the resolution of acute inflammation remains to be elucidated. This study uses a cell-based approach to unveil their molecular bases.
methodsAll-trans retinoic acid-differentiated HL-60 cells (dHL-60) served as surrogate PMNs. NET release from MSU-activated dHL-60 was confirmed by detecting DNA, neutrophil elastase, and citrullinated histone 3, forming large NET-MSU aggregates. NET area was measured with Fiji software after SYTOX Green staining. Released pro-inflammatory cytokines IL-8 and TNF-α, and the anti-inflammatory cytokine IL-1RA in culture supernatants were quantified to calculate the estimate inflammation score (EIS). Cellular redox state was determined by a FRET-based sensor. Expression of intracellular positive (ERK1/2) and negative (SHP-1 and SHIP-1) cytokine signaling regulators was detected by western blot. qPCR detected mRNA expressions of CISH and SOCS1-SOCS7. Flow cytometry measured neutrophil N1 (CD54) and N2 (CD182) surface markers after staining with fluorescent-conjugated antibodies.
resultsIncubating dHL-60 with MSU for 4 h maximized NET-MSU aggregate formation and acute inflammation with an EIS of 11.6. Prolonging the incubation of dHL-60 + MSU to 22 h gradually raised the EIS to 19.40 without increasing NET area, due to reduced cellular redox capacity. Adding both new dHL-60 and new MSU crystals to the culture, mimicking the clinical scenario, increased NET area but conversely suppressed EIS to 1.53, indicating acute inflammation resolution. The resolution of acute inflammation following prolonged incubation was attributed to decreases in P-ERK and increases in P-SHP-1, SOCS2, SOCS3, and CISH gene expressions, which may suppress pro-inflammatory and enhance anti-inflammatory cytokine production. Moreover, the large NET-MSU aggregates facilitated N1 to N2 polarization, crucial for accelerating inflammation resolution.
conclusionWe explored the potential molecular basis for the spontaneous resolution of MSU induced acute inflammation using a cell-based model in that huge NET-MSU aggregates frustrate the transformation of newly entering PMNs to the N2 phenotype, enhancing the production of the anti-inflammatory cytokine IL-1RA.
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