ArticleArthritis and rheumatism2013
P2X7 blockade attenuates murine lupus nephritis by inhibiting activation of the NLRP3/ASC/caspase 1 pathway.
Article in Arthritis and rheumatism, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 109 papers.
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Who cites it
109 citing papers in PubMed, 186 citations in OpenAlex.
- ATP is not always pro-inflammatory: rethinking purinergic signalling in cancer and autoimmunity.Purinergic signalling · 2026Review
- Cells' survival pattern of kidney macrophages and epithelial cells in lupus nephritis is influenced by glycolysis.Lupus science & medicine · 2026Article
- The TRAF6-TXNIP-NLRP3 signaling axis regulates LPS-induced pyroptosis in glomerular podocytes.Journal of molecular histology · 2026Article
- NLRP3 Inflammasome as Potential Predictor of Non-Responsiveness to Immunosuppressive Treatment in Lupus Nephritis.International journal of molecular sciences · 2025Article
- Recent insights into the role of innate immunity in lupus.Human molecular genetics · 2025Review
- Resveratrol Alleviates Inflammatory Response Through P2X7/NLRP3 Signaling Pathway: In Silico and In Vitro Evidence from Activated Microglia.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Purinoreceptor P2X7 in Extracellular ATP-Mediated Inflammation through the Spectrum of Kidney Diseases and Kidney Transplantation.Journal of the American Society of Nephrology : JASN · 2025Review
- Induction of LY6E regulates interleukin-1β production, potentially contributing to the immunopathogenesis of systemic lupus erythematosus.Cell communication and signaling : CCS · 2025Article
- ATP/P2X7 receptor/NLRP3 pathway facilitates renal tubular epithelial-myofibroblast transdifferentiation and interstitial fibrosis in rats with unilateral ureteral obstruction.Frontiers in pharmacology · 2025Article
- Targeting the NLRP3 inflammasome in kidney disease: molecular mechanisms, pathogenic roles, and emerging small-molecule therapeutics.Frontiers in immunology · 2025Review
- An improved understanding of pediatric chronic nonbacterial osteomyelitis pathophysiology informs current and future treatment.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2024Review
- NLRP3-mediated IL-1β in regulating the imbalance between Th17 and Treg in experimental autoimmune prostatitis.Scientific reports · 2024Article
- Pharmacological interaction and immune response of purinergic receptors in therapeutic modulation.Purinergic signalling · 2024Review
- P2 X 7 receptor is a critical regulator of extracellular ATP-induced profibrotic genes expression in rat kidney: implication of transforming growth factor-β/Smad signaling pathway.Purinergic signalling · 2024Article
- Long non-coding RNA ENSMUST00000197208 promotes a shift in the Th17/Treg ratio via the P2X7R-NLRP3 inflammasome axis in collagen-induced arthritis.Immunologic research · 2024Article
- Research Progress of Pyroptosis in Renal Diseases.Current medicinal chemistry · 2024Review
- The P2X7 Receptor in Autoimmunity.International journal of molecular sciences · 2023Review
- Upregulation of P2X7 Exacerbates Myocardial Ischemia-Reperfusion Injury through Enhancing Inflammation and Apoptosis in Diabetic Mice.Journal of immunology (Baltimore, Md. : 1950) · 2023Article
- NAMPT is a metabolic checkpoint of IFNγ-producing CD4Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
- The regulation of self-tolerance and the role of inflammasome molecules.Frontiers in immunology · 2023Review
49 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
objectiveThe NLRP3 inflammasome plays key roles in inflammation and autoimmunity, and purinergic receptor P2X7 has been proposed to be upstream of NLRP3 activation. The aim of the present study, using murine models, was to investigate whether the P2X7 /NLRP3 inflammasome pathway contributes to the pathogenesis of lupus nephritis (LN).
methodsMRL/lpr mice were treated with the selective P2X7 antagonist brilliant blue G (BBG) for 8 weeks. Following treatment, the severity of renal lesions, production of anti-double-stranded DNA (anti-dsDNA) antibodies, rate of survival, activation of the NLRP3/ASC/caspase 1 inflammasome pathway, and ratio of Th17 cells to Treg cells were evaluated. P2X7 -targeted small interfering RNA (siRNA) was also used for in vivo intervention. Similar evaluations were carried out in NZM2328 mice, a model of LN in which the disease was accelerated by administration of adenovirus-expressing interferon-α (AdIFNα).
resultsSignificant up-regulation of P2X7 /NLRP3 inflammasome signaling molecules was detected in the kidneys of MLR/lpr mice as compared with normal control mice. Blockade of P2X7 activation by BBG suppressed NLRP3/ASC/caspase 1 assembly and the subsequent release of interleukin-1β (IL-1β), resulting in a significant reduction in the severity of nephritis and circulating anti-dsDNA antibodies. The lifespan of the treated mice was significantly prolonged. BBG treatment reduced the serum levels of IL-1β and IL-17 and the Th17:Treg cell ratio. Similar results were obtained by specific siRNA silencing of P2X7 in vivo. The effectiveness of BBG treatment in modulating LN was confirmed in NZM2328 mice with AdIFNα-accelerated disease.
conclusionActivation of the P2X7 signaling pathway accelerates murine LN by activating the NLRP3/ASC/caspase 1 inflammasome, resulting in increased IL-1β production and enhanced Th17 cell polarization. Thus, targeting of the P2X7 /NLRP3 pathway should be considered as a novel therapeutic strategy in patients with lupus.
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