ArticleActa pharmacologica Sinica2022
Gout-associated monosodium urate crystal-induced necrosis is independent of NLRP3 activity but can be suppressed by combined inhibitors for multiple signaling pathways.
Article in Acta pharmacologica Sinica, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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33 citing papers in PubMed, 26 citations in OpenAlex.
- Monosodium urate crystals induce lytic macrophage death partially dependent on both pyroptosis and necroptosis.Clinical rheumatology · 2026Article
- Cascade Nanozyme-Catalyzed Tophi Dissolution and ROS Scavenging for Anti-Inflammatory Therapy in Gouty Arthritis.Small (Weinheim an der Bergstrasse, Germany) · 2026Article
- RepurposingACS omega · 2026Article
- ORF3 protein of porcine circovirus type 2 induced RIPK3 phosphorylation-driven autophagy to promote viral replication.Scientific reports · 2026Article
- Tranilast ameliorates experimental abdominal aortic aneurysm by inhibiting the NLRP3 inflammasome pathway.Journal of pharmaceutical analysis · 2026Article
- Establishment and phenotypic characterization of a rat model with a clinically relevant phenotype for chronic gouty arthritis.Frontiers in immunology · 2026Article
- Regulatory mechanisms of programmed cell death in hyperuricaemia and their disease relevance.Frontiers in cell and developmental biology · 2026Review
- The interplay between NLRP3 inflammasome and metabolic signals in gouty arthritis.Frontiers in immunology · 2026Review
- Alpha-1 Antitrypsin Mediates Spontaneous Resolution of Acute Gouty Inflammation Via Inhibiting Caspase 3/GSDME-dependent Macrophage Pyroptosis.Inflammation · 2025Article
- NLRP3-Mediated PANoptosis and Associated Interventions in Endothelial Injury.Cardiovascular toxicology · 2025Review
- Differences in macrophage pyroptosis and polarization induced by nano-/micro-calcium oxalate crystals.Journal of nanobiotechnology · 2025Article
- Correlation of the lipid complex marker hs-CRP/HDL-C ratio with hyperuricaemia: a cross-sectional retrospective study from NHANES 2015-2018.Scientific reports · 2025Article
- Global, regional, and national burden of gout among older adults (≥65) from 1990 to 2021 and projections for 2050.Frontiers in public health · 2025Article
- Effects of Baicalin on Gout Based on Network Pharmacology, Molecular Docking, and in vitro Experiments.Journal of inflammation research · 2025Article
- Macrophage targeting precision nanomedicine utilizing ROS-responsive metallozyme-loaded nanomicelle for enhanced treatment of gout-induced inflammation.Science and technology of advanced materials · 2025Article
- Innate immune sensing of cell death in disease and therapeutics.Nature cell biology · 2024Review
- Hyperuricemia and its related diseases: mechanisms and advances in therapy.Signal transduction and targeted therapy · 2024Review
- Ferroptosis in Arthritis: Driver of the Disease or Therapeutic Option?International journal of molecular sciences · 2024Review
- Britannin as a novel NLRP3 inhibitor, suppresses inflammasome activation in macrophages and alleviates NLRP3-related diseases in mice.Acta pharmacologica Sinica · 2024Article
- Blocking reverse electron transfer-mediated mitochondrial DNA oxidation rescues cells from PANoptosis.Acta pharmacologica Sinica · 2024Article
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Monosodium urate (MSU) crystals, the etiological agent of gout, are formed in joints and periarticular tissues due to long-lasting hyperuricemia. Although MSU crystal-triggered NLRP3 inflammasome activation and interleukin 1β (IL-1β) release are known to have key roles in gouty arthritis, recent studies revealed that MSU crystal-induced necrosis also plays a critical role in this process. However, it remains unknown what forms of necrosis have been induced and whether combined cell death inhibitors can block such necrosis. Here, we showed that MSU crystal-induced necrosis in murine macrophages was not dependent on NLRP3 inflammasome activation, as neither genetic deletion nor pharmacological blockade of the NLRP3 pathway inhibited the necrosis. Although many cell death pathways (such as ferroptosis and pyroptosis) inhibitors or reactive oxygen species inhibitors did not have any suppressive effects, necroptosis pathway inhibitors GSK'872 (RIPK3 inhibitor), and GW806742X (MLKL inhibitor) dose-dependently inhibited MSU crystal-induced necrosis. Moreover, a triple combination of GSK'872, GW806742X, and IDN-6556 (pan-caspase inhibitor) displayed enhanced inhibition of the necrosis, which was further fortified by the addition of MCC950 (NLRP3 inhibitor), suggesting that multiple cell death pathways might have been triggered by MSU crystals. Baicalin, a previously identified inhibitor of NLRP3, inhibited MSU crystal-induced inflammasome activation and suppressed the necrosis in macrophages. Besides, baicalin gavage significantly ameliorated MSU crystal-induced peritonitis in mice. Altogether, our data indicate that MSU crystals induce NLRP3-independent necrosis, which can be inhibited by combined inhibitors for multiple signaling pathways, highlighting a new avenue for the treatment of gouty arthritis.
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