ArticleJournal of the American Society of Nephrology : JASN2015
Phagocyte NADPH oxidase restrains the inflammasome in ANCA-induced GN.
Article in Journal of the American Society of Nephrology : JASN, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 38 citations in OpenAlex.
- NOX2 deficiency exacerbates lupus nephritis through activation of NLRP3 inflammasome in neutrophils.Journal of biomedical science · 2026Article
- Soluble CD95L triggers Caspase-10-driven reactive oxygen species production in neutrophils and aggravates anti-neutrophil cytoplasmic antibody-vasculitis.Nature communications · 2026Article
- The type 1 and type 3 immune responses underlying the tissue inflammation associated with NOX2 deficiency.Frontiers in immunology · 2026Review
- NLRP3 inflammasome activity and pyroptosis are involved in CD206Acta biochimica et biophysica Sinica · 2025Article
- Chronic granulomatous disease: lessons in cell biology from monogenic immunodeficiency.Clinical and experimental immunology · 2025Review
- βFrontiers in immunology · 2024Article
- Novel Therapies for ANCA-associated Vasculitis: Apilimod Ameliorated Endothelial Cells Injury through TLR4/NF-κB Pathway and NLRP3 Inflammasome.Current pharmaceutical design · 2024Article
- CSF2-dependent monocyte education in the pathogenesis of ANCA-induced glomerulonephritis.Annals of the rheumatic diseases · 2022Article
- The Role of Inflammasomes in Glomerulonephritis.International journal of molecular sciences · 2022Review
- Genetic Background but Not Intestinal Microbiota After Co-Housing Determines Hyperoxaluria-Related Nephrocalcinosis in Common Inbred Mouse Strains.Frontiers in immunology · 2021Article
- Neutrophil Gelatinase-Associated Lipocalin Protects from ANCA-Induced GN by Inhibiting TJournal of the American Society of Nephrology : JASN · 2020Article
- Clonal hematopoiesis in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis.Haematologica · 2020Article
- Therapeutic targeting of neutrophil exocytosis.Journal of leukocyte biology · 2020Review
- The expression of NOD2, NLRP3 and NLRC5 and renal injury in anti-neutrophil cytoplasmic antibody-associated vasculitis.Journal of translational medicine · 2019Article
- Endothelium structure and function in kidney health and disease.Nature reviews. Nephrology · 2019Review
- Thioredoxin-interacting protein deficiency ameliorates kidney inflammation and fibrosis in mice with unilateral ureteral obstruction.Laboratory investigation; a journal of technical methods and pathology · 2018Article
- Re-Examining Neutrophil Participation in GN.Journal of the American Society of Nephrology : JASN · 2017Review
- Of Inflammasomes and Alarmins: IL-1β and IL-1α in Kidney Disease.Journal of the American Society of Nephrology : JASN · 2016Review
- Impaired phagocytosis and reactive oxygen species production in phagocytes is associated with systemic vasculitis.Arthritis research & therapy · 2016Article
- Neutrophils in animal models of autoimmune disease.Seminars in immunology · 2016Review
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
ANCA-activated phagocytes cause vasculitis and necrotizing crescentic GN (NCGN). ANCA-induced phagocyte NADPH oxidase (Phox) may contribute by generating tissue-damaging reactive oxygen species. We tested an alternative hypothesis, in which Phox restrains inflammation by downregulating caspase-1, thereby reducing IL-1β generation and limiting NCGN. In an antimyeloperoxidase (anti-MPO) antibody-mediated disease model, mice transplanted with either gp91(phox)-deficient or p47(phox)-deficient bone marrow showed accelerated disease with increased crescents, necrosis, glomerular monocytes, and renal IL-1β levels compared with mice transplanted with wild-type bone marrow. IL-1β receptor blockade abrogated aggravated NCGN in gp91(phox)-deficient mice. In vitro, challenge with anti-MPO antibody strongly enhanced caspase-1 activity and IL-1β generation in gp91(phox)-deficient and p47(phox)-deficient monocytes compared with wild-type monocytes. This enhanced IL-1β generation was abrogated when caspase-1 was blocked. ANCA-induced superoxide and IL-1β generation were inversely related in human monocytes. Furthermore, transplantation of gp91(phox)/caspase-1 double-deficient bone marrow rescued the accelerated NCGN phenotype in gp91(phox) bone marrow-deficient mice. These results suggest that Phox-generated reactive oxygen species downregulate caspase-1, thereby keeping the inflammasome in check and limiting ANCA-induced inflammation. IL-1 receptor blockade may provide a promising strategy in NCGN, whereas our data question the benefit of antioxidants.
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