ArticleNature communications2012
Extracellular Ca2+ is a danger signal activating the NLRP3 inflammasome through G protein-coupled calcium sensing receptors.
Article in Nature communications, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 253 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
253 citing papers in PubMed, 1 synthesis or guideline pooled it, 473 citations in OpenAlex.
- The calcium-sensing receptor in sepsis and septic shock, mechanistic pathways and translational perspectives: a systematic review.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Pooled it
- Trial
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- PLCG1 regulates pyroptosis to inhibit the progression of non-small cell lung cancer: A Mendelian randomization study.Medicine · 2026Article
- Cobalt-mediated suppression of IFN-γ-JAK-STAT1 signaling reprograms IDO1-driven immunosuppression for metalloimmunotherapy.Science advances · 2026Article
- Oxidative Stress and Mitochondrial Dysfunction in Chronic Kidney Disease: From Molecular Mechanisms to Biomarkers and Targeted Therapies.Antioxidants (Basel, Switzerland) · 2026Review
- Damage-Associated Molecular Patterns in Mesothelioma: Drivers of Inflammation and Therapeutic Targets.International journal of molecular sciences · 2026Review
- Targeting Gasdermins for Therapeutic Interventions in Central Nervous System Injury.Neurotoxicity research · 2026Review
- A Review on Structural Insights into NLRP3 and NEK7: Domain Architecture, Subcellular Localization, and Their Interaction in Inflammasome Assembly and Signaling.Molecular neurobiology · 2026Review
- An "old" cytokine's new trick: IL-1β in B cells and the germinal center.Function (Oxford, England) · 2026Review
- NLRP3 inflammasome promotes PAD2/PAD4 release and protein citrullination in rheumatoid arthritis.Communications biology · 2026Article
- Plasma SERPINA3 and its clinical correlates in adolescent major depressive disorder: an exploratory case-control study.BMC psychiatry · 2026Article
- DAMP signaling networks: from receptors to diverse pathophysiological functions.Journal of advanced research · 2026Review
- Activation of the NLRP3 inflammasome in osteoclasts is suppressed by a Tmem178-dependent mechanism that restricts CaScience signaling · 2026Article
- Article
- NCX1 reverse mode promotes calcium-dependent Neutrophil Extracellular Trap formation and lung damage in chronic obstructive pulmonary disease.Nature communications · 2026Article
- Deficiency of lysosomal TMEM175 in myeloid macrophages exerts anti-tumor immunity via inflammasome and cross-presentation pathway.Nature communications · 2026Article
- Endoplasmic Reticulum Redoxome: Protein Folding and Beyond.Biochemistry · 2026Review
- Microbial sensing through the non-canonical inflammasome modulates airway type 2 immunity.Frontiers in immunology · 2026Article
- Calcimimetics and CaSR signaling in CKD-MBD: bone-immune-vascular crosstalk and therapeutic potential.Frontiers in immunology · 2026Review
193 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Activation of the NLRP3 inflammasome enables monocytes and macrophages to release high levels of interleukin-1β during inflammatory responses. Concentrations of extracellular calcium can increase at sites of infection, inflammation or cell activation. Here we show that increased extracellular calcium activates the NLRP3 inflammasome via stimulation of G protein-coupled calcium sensing receptors. Activation is mediated by signalling through the calcium-sensing receptor and GPRC6A via the phosphatidyl inositol/Ca(2+) pathway. The resulting increase in the intracellular calcium concentration triggers inflammasome assembly and Caspase-1 activation. We identified necrotic cells as one source for excess extracellular calcium triggering this activation. In vivo, increased calcium concentrations can amplify the inflammatory response in the mouse model of carrageenan-induced footpad swelling, and this effect was inhibited in GPRC6A(-/-) mice. Our results demonstrate that G-protein-coupled receptors can activate the inflammasome, and indicate that increased extracellular calcium has a role as a danger signal and amplifier of inflammation.
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Registered trials
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.