ArticlePloS one2012
Common genetic variations in the NALP3 inflammasome are associated with delayed apoptosis of human neutrophils.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 41 citations in OpenAlex.
- CARD8: A Novel Inflammasome Sensor with Well-Known Anti-Inflammatory and Anti-Apoptotic Activity.Cells · 2024Review
- House ammonia exposure causes alterations in microbiota, transcriptome, and metabolome of rabbits.Frontiers in microbiology · 2023Article
- RAGE contributes to allergen driven severe neutrophilic airway inflammationFrontiers in immunology · 2023Article
- Galectin-3: a new biomarker for differentiating periodic fever, adenitis, pharyngitis, aphthous stomatitis (PFAPA) syndrome from familial Mediterranean fever?Rheumatology international · 2022Observational
- Review
- Gain-of-Function Polymorphisms in Human Inflammasomes: Implications for Cystic Fibrosis.American journal of respiratory cell and molecular biology · 2021Article
- Article
- A NovelDiagnostics (Basel, Switzerland) · 2020Article
- Total saponin of Dioscorea collettii attenuates MSU crystal‑induced inflammation via inhibiting the activation of the NALP3 inflammasome and caspase‑1 in THP‑1 macrophages.Molecular medicine reports · 2020Article
- Increased Prevalence ofFrontiers in immunology · 2020Observational
- Inhibition of integrin α5β1 ameliorates VEGF-induced retinal neovascularization and leakage by suppressing NLRP3 inflammasome signaling in a mouse model.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2018Article
- Polymorphisms and expression of inflammasome genes are associated with the development and severity of rheumatoid arthritis in Brazilian patients.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2018Article
- Mutational profile of rare variants in inflammasome-related genes in Behçet disease: A Next Generation Sequencing approach.Scientific reports · 2017Article
- Genetic Polymorphisms in Inflammasome-Dependent Innate Immunity among Pediatric Patients with Severe Renal Parenchymal Infections.PloS one · 2015Article
- Genetic profiling of autoinflammatory disorders in patients with periodic fever: a prospective study.Pediatric rheumatology online journal · 2015Article
- NLRP3 inflammasome sequential changes in Staphylococcus aureus-induced mouse model of acute rhinosinusitis.International journal of molecular sciences · 2014Article
- C10X polymorphism in the CARD8 gene is associated with bacteraemia.Immunity, inflammation and disease · 2014Article
- Chrysophanol inhibits NALP3 inflammasome activation and ameliorates cerebral ischemia/reperfusion in mice.Mediators of inflammation · 2014Article
- Anti-TNF treatment response in rheumatoid arthritis patients is associated with genetic variation in the NLRP3-inflammasome.PloS one · 2014Article
- Article
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundNeutrophils are key-players in the innate host defense and their programmed cell death and removal are essential for efficient resolution of inflammation. These cells recognize a variety of pathogens, and the NOD-like receptors (NLRs) have been suggested as intracellular sensors of microbial components and cell injury/stress. Some NLR will upon activation form multi-protein complexes termed inflammasomes that result in IL-1β production. NLR mutations are associated with auto-inflammatory syndromes, and our previous data propose NLRP3 (Q705K)/CARD-8 (C10X) polymorphisms to contribute to increased risk and severity of inflammatory disease by acting as genetic susceptibility factors. These gene products are components of the NALP3 inflammasome, and approximately 6.5% of the Swedish population are heterozygote carriers of these combined gene variants. Since patients carrying the Q705K/C10X polymorphisms display leukocytosis, the aim of the present study was to find out whether the inflammatory phenotype was related to dysfunctional apoptosis and impaired clearance of neutrophils by macrophages. METHODS AND
findingsPatients carrying the Q705K/C10X polymorphisms displayed significantly delayed spontaneous as well as microbe-induced apoptosis compared to matched controls. Western blotting revealed increased levels and phosphorylation of Akt and Mcl-1 in the patients' neutrophils. In contrast to macrophages from healthy controls, macrophages from the patients produced lower amounts of TNF; suggesting impaired macrophage clearance response.
conclusionsThe Q705K/C10X polymorphisms are associated with delayed apoptosis of neutrophils. These findings are explained by altered involvement of different regulators of apoptosis, resulting in an anti-apoptotic profile. Moreover, the macrophage response to ingestion of microbe-induced apoptotic neutrophils is altered in the patients. Taken together, the patients display impaired turnover and clearance of apoptotic neutrophils, pointing towards a dysregulated innate immune response that influences the resolution of inflammation. The future challenge is to understand how microbes affect the activation of inflammasomes, and why this interaction will develop into severe inflammatory disease in certain individuals.
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