ArticleFrontiers in immunology2019
Cytokine Production and NET Formation by Monosodium Urate-Activated Human Neutrophils Involves Early and Late Events, and Requires Upstream TAK1 and Syk.
Article in Frontiers in immunology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 43 citations in OpenAlex.
- Neutrophil Fate and Function in Gout: From Sterile Inflammation to Resolution.International journal of molecular sciences · 2026Review
- Neutrophil extracellular traps in gout: from immune defense to pathological dynamic equilibrium.Frontiers in immunology · 2026Review
- NETosis-specific cell death: a novel mechanism in the pathogenesis of gouty arthritis.European journal of medical research · 2025Review
- Reactive Oxygen Species Across Death Pathways: Gatekeepers of Apoptosis, Ferroptosis, Pyroptosis, Paraptosis, and Beyond.International journal of molecular sciences · 2025Review
- Review
- Neutrophil Extracellular Trap Formation Model Induced by Monosodium Urate and Phorbol Myristate Acetate: Involvement in MAPK Signaling Pathways.International journal of molecular sciences · 2024Article
- Targeting Neutrophil Extracellular Traps in Gouty Arthritis: Insights into Pathogenesis and Therapeutic Potential.Journal of inflammation research · 2024Review
- CREB1-driven CXCR4Nature communications · 2023Article
- Myeloid Src-family kinases are critical for neutrophil-mediated autoinflammation in gout and motheaten models.The Journal of experimental medicine · 2023Article
- Asymptomatic hyperuricaemia in chronic kidney disease: mechanisms and clinical implications.Clinical kidney journal · 2023Review
- Phosphoinositol 3-kinase-driven NET formation involves different isoforms and signaling partners depending on the stimulus.Frontiers in immunology · 2023Article
- The Independent Value of Neutrophil to Lymphocyte Ratio in Gouty Arthritis: A Narrative Review.Journal of inflammation research · 2023Review
- Human Neutrophils Generate Extracellular Vesicles That Modulate Their Functional Responses.Cells · 2022Article
- Neutrophil extracellular traps induce the bone erosion of gout.BMC musculoskeletal disorders · 2022Article
- Article
- Role of Cellular Metabolism in the Formation of Neutrophil Extracellular Traps in Airway Diseases.Frontiers in immunology · 2022Review
- Identification of renal ischemia reperfusion injury subtypes and predictive strategies for delayed graft function and graft survival based on neutrophil extracellular trap-related genes.Frontiers in immunology · 2022Article
- Tetrandrine Ameliorates Rheumatoid Arthritis in Mice by Alleviating Neutrophil Activities.Evidence-based complementary and alternative medicine : eCAM · 2022Article
- The Role of CD147 in Pathological Cardiac Hypertrophy Is Regulated by Glycosylation.Oxidative medicine and cellular longevity · 2022Article
- Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Gout is a prevalent and incapacitating disease triggered by the deposition of monosodium urate (MSU) crystals in joints, which are also massively infiltrated by neutrophils. The interaction of the latter with MSU crystals triggers several responses, including the generation of inflammatory mediators and of neutrophil extracellular traps (NETs). Though some of the signaling events mobilized by MSU in neutrophils have been described (e.g., Src family kinases, Syk, PKC, PI3K), the picture remains fragmentary. Likewise, the impact of these signaling events on cellular responses is incompletely understood. In this study, we examined transcriptomic changes triggered by MSU in neutrophils and their impact on the corresponding proteins, as well as the role of various signaling pathways in prominent functional responses. We report for the first time that neutrophils can secrete the monocyte chemoattractant, CCL4, in response to MSU. Accordingly, we found that transcription factors NF-κB, CREB, and C/EBP are belatedly activated by MSU crystals, and at least the former is involved in chemokine generation. Moreover, we show that MAPKs and Akt are activated by MSU in neutrophils, that they are under the control of TAK1 and Syk, and that they participate in cytokine generation and NETosis. In the latter instance, we found the phenomenon to be independent of endogenous ROS, but under the control of PAD4. We finally provide evidence that endogenous factors contribute to the belated phosphorylation of kinases and transcription factors in response to MSU. Collectively, our findings unveil potentially important therapeutic targets for gouty arthritis.
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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.