ArticleNature communications2024
Activation of osmo-sensitive LRRC8 anion channels in macrophages is important for micro-crystallin joint inflammation.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- HIF-1α in CD4Journal of pharmaceutical analysis · 2026Article
- Disruption of macrophage cell volume drives inflammatory responses and type I interferon signaling.The Journal of cell biology · 2026Article
- Endothelial LRRC8C Associates With LRRC8A and LRRC8B to Regulate Vascular Reactivity and Blood Pressure.Hypertension (Dallas, Tex. : 1979) · 2026Article
- Mechanosensitive ion channels as novel targets in osteoporosis.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2026Review
- Spermidine Reproduces the Anti-Inflammatory Effects of Intermittent Fasting and Prevents Urate and Calcium Pyrophosphate Crystal-Induced Inflammation.Arthritis & rheumatology (Hoboken, N.J.) · 2026Article
- Gout and NLRP3 Inflammasome Biology.Arthritis & rheumatology (Hoboken, N.J.) · 2025Review
- Intra-articular sustained-release colchicine is efficacious in an inflammatory arthritis rat model.RMD open · 2025Article
- Transcriptional Repression of CCL2 by KInternational journal of molecular sciences · 2025Article
- State of the art indicators for imaging purinergic dynamics in vitro and in vivo.Purinergic signalling · 2025Review
- NLRP3 Inflammasome-Mediated Pyroptosis in Osteoporosis: Osteoimmune Mechanisms and Therapeutic Targeting.Journal of cellular and molecular medicine · 2025Review
- Updated insights into the molecular networks for NLRP3 inflammasome activation.Cellular & molecular immunology · 2025Review
- A systems immunology perspective on gout pathogenesis and its precision-targeted treatment strategies.Frontiers in immunology · 2025Review
- Establishment and evaluation of a model for clinical feature selection and prediction in gout patients with cardiovascular diseases: a retrospective cohort study.Frontiers in endocrinology · 2025Article
Corrections and comments
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Authors and funding
16 authors.
Funding
Abstract
Deposition of monosodium urate and calcium pyrophosphate (MSU and CPP) micro-crystals is responsible for painful and recurrent inflammation flares in gout and chondrocalcinosis. In these pathologies, the inflammatory reactions are due to the activation of macrophages responsible for releasing various cytokines including IL-1β. The maturation of IL-1β is mediated by the multiprotein NLRP3 inflammasome. Here, we find that activation of the NLRP3 inflammasome by crystals and concomitant production of IL-1β depend on cell volume regulation via activation of the osmo-sensitive LRRC8 anion channels. Both pharmacological inhibition and genetic silencing of LRRC8 abolish NLRP3 inflammasome activation by crystals in vitro and in mouse models of crystal-induced inflammation. Activation of LRRC8 upon MSU/CPP crystal exposure induces ATP release, P2Y receptor activation and intracellular calcium increase necessary for NLRP3 inflammasome activation and IL-1β maturation. We identify a function of the LRRC8 osmo-sensitive anion channels with pathophysiological relevance in the context of joint crystal-induced inflammation.
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