NLRP3


NLR family pyrin domain containing 3


Gene Context Sentence


Table 2. Analysis of context sentence of NLRP3 gene in 49 abstracts.

PMID Gene Context Sentence
32251729 Among its potential mechanisms of action is the non-selective inhibition of NLRP3 inflammasome which is thought to be a major pathophysiologic component in the clinical course of patients with COVID-19.
32365944 Moreover, SUD-MC actuated NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome-dependent pulmonary inflammation, as confirmed by the NLRP3 inflammasome inhibitor and the NLRP3-/- mouse model. […] This study demonstrated that SARS-CoV SUD modulated NLRP3 inflammasome-dependent CXCL10-mediated pulmonary inflammation, providing the potential therapeutic targets for developing the antiviral agents.
32430627 We will focus on aging, cytokine storm, NLRP3/inflammasome, hypoxemia, and air pollution, which is an emerging cardiovascular risk factor associated with rapid urbanization and globalization.
32459524 The production of increased amounts of cytokines such as TNF-α, IL-1, IL-6 and MCP-1 lead to oxidative stress and defective function of innate and adaptive immunity, while the activation of NLRP3 inflammasome seems to play a crucial role in the pathogenesis of the infection.
32482538 This process is an inflammatory picture, involving an NLRP3 inflamosome-triggered cytokine storm, the main player in alveolar destruction.
32504923 NAC has also been shown to inhibit the NLRP3 inflammasome pathway (IL1β and IL18) in vitro, and decrease plasma TNF-ɑ in human clinical trials.
32505910 IL-1β is generated by macrophages upon activation of intracellular NLRP3 (NOD-like, leucine rich repeat domains, and pyrin domain-containing protein 3), part of the functional NLRP3 inflammasome complex that detects pathogenic microorganisms and stressors, while neutrophils are enhanced by increasing levels of IL-1β. […] Herein, we present arguments underlying our hypothesis that IL-1β and NETs, mediated via NLRP3 inflammasomes, form a feed-forward loop leading to the excessive alveolar and endothelial damage observed in severe cases of COVID-19.
32562276 The well-known anti-inflammatory properties of statins, by blocking several molecular mechanisms, including NF-κB and NLRP3 inflammasome, could limit the “cytokine storm” in severe COVID-19 patients which is linked to fatal outcome.
32626733 We also evaluated pyroptosis (NLRP3, caspase-1), apoptosis (caspase-3, caspase-8), proinflammatory (TNF-α, IL-1β, and IL-6)-related protein and gene expression levels. […] It also significantly inhibited the high levels of NLRP3, caspase-1, caspase-3, caspase-8, TNF-α, IL-1β, and IL-6 induced by CLP.
32639511 Participants with DNMT3A or TET2 CHIP-driver sequence variations displayed increased expression of interleukin 1β (no CHIP-driver sequence variations, 1.6217 normalized Unique Molecular Identifiers [nUMI]; DNMT3A, 5.3956 nUMI; P < .001; TET2, 10.8216 nUMI; P < .001), the interleukin 6 receptor (no CHIP-driver sequence variations, 0.5386 nUMI; DNMT3A, 0.9162 nUMI; P < .001;TET2, 0.5738 nUMI; P < .001), as well as the NLRP3 inflammasome complex (no CHIP-driver sequence variations, 0.4797 nUMI; DNMT3A, 0.9961 nUMI; P < .001; TET2, 1.2189 nUMI; P < .001), plus upregulation of CD163 (no CHIP-driver sequence variations, 0.5239 nUMI; DNMT3A, 1.4722 nUMI; P < .001; TET2, 1.0684 nUMI; P < .001), a cellular receptor capable of mediating infection, macrophage activation syndrome, and other genes involved in cytokine response syndrome.
32655582 This pathology is characterized by intense, rapid stimulation of the innate immune response that triggers activation of the Nod-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome pathway and release of its products including the proinflammatory cytokines IL-6 and IL-1β. […] Here we review the literature that describes the pathogenesis of severe COVID-19 and NLRP3 activation and describe an important role in targeting this pathway for the treatment of severe COVID-19.
32670297 SARS-CoV-2 might directly activate NLRP3 inflammasome resulting in an endogenous adjuvant activity necessary to mount a proper adaptive immune response against the virus. […] Heterogeneous response of COVID-19 patients could be attributed to differences in not being able to properly downregulate NLRP3 inflammasome activation. […] Patients with a reduced immune fitness can demonstrate a dysregulated NLRP3 inflammasome activity resulting in severe COVID-19 with tissue damage and a cytokine storm.
32691370 Moreover, we demonstrate for the first time that, in human VSELs and HSCs, the interaction of the ACE2 receptor with the SARS-CoV-2 spike protein activates the Nlrp3 inflammasome, which if hyperactivated may lead to cell death by pyroptosis. […] •Interaction of viral spike protein with ACE2 receptor may hyperactivate Nlrp3 inflammasome which induces cell death by pyroptosis. […] •What is not shown since these cells express also Ang II receptor they may hyperactivate Nlrp3 inflammasome in response to Ang II which may induce pyroptosis.
32693241 IL-6 and NLRP3 inflammasome are the major immune components in immune responses stimulation upon pathogen infection. […] In this review we discuss the potential impact of IL-6 and NLRP3 inflammasome blocker drugs on inflammatory responses, viral clearance, and pathological and clinical manifestations.
32734714 This review considers several mechanisms of SARS-CoV-2 innate immune evasion including suppression of IFN-α/β production at the earliest stage of infection, mechanisms that exhaust natural killer cell-mediated cytotoxicity, overstimulation of NLRP3 inflammasome and induction of a cytokine storm.
32763970 Here we demonstrate that infection with the murine coronavirus mouse hepatitis virus (MHV) activated the NLRP3 inflammasome and inflammatory cell death in the form of PANoptosis. […] Deleting NLRP3 inflammasome components or the downstream cell death executioner gasdermin D (GSDMD) led to an initial reduction in cell death followed by a robust increase in the incidence of caspase-8- and receptor-interacting serine/threonine-protein kinase 3 (RIPK3)-mediated inflammatory cell deathafter coronavirus infection. […] Additionally, loss of GSDMD promoted robust NLRP3 inflammasome activation. […] Altogether, our findings show that inflammatory cell death, PANoptosis, is induced by coronavirus infection and that impaired NLRP3 inflammasome function or pyroptosis can lead to negative consequences for the host.
32765942 Recent studies suggest a role for the nucleotide-binding domain and leucine rich repeat containing family, pyrin domain containing 3 (NLRP3) inflammasome activation in lung inflammation and fibrosis in SARS-CoV and SARS-CoV-2 infections. […] Increased NLRP3/ apoptosis-associated speck-like protein (ASC) mRNA expression and increased caspase-1 activity, have been observed in aged lung, provoking increased and heightened expression levels of mature Interleukin (IL)-1β and IL-18 in aged individuals. […] NLRP3 inflammasome is over-activated in aged individuals, through deficient mitochondrial functioning, increased mitochondrial Reactive Oxigen Species (mtROS) and/or mitochondrial (mt)DNA, leading to a hyper-response of classically activated macrophages and subsequent increases in IL-1 β. […] This NLRP3 over-activated status in elderly individuals, is also observed in telomere dysfunctional mice models. […] In our opinion, the NLRP3 inflammasome plays a central role in the increased lethality observed in elderly patients infected by COVID-19.
32776354 The NLRP3 inflammasome is a master regulator of metaflammation and has a pivotal role in the pathophysiology of either obesity or diabetes. […] Here, we discuss the most recent findings suggesting contribution of NLRP3 inflammasome to the increase in complications in COVID-19 patients with diabesity. […] We also review current pharmacological strategies for COVID-19, focusing on treatments whose efficacy could be due, at least in part, to interference with the activation of the NLRP3 inflammasome.
32797724 The most investigated is the NLRP3 inflammasome, which can be activated by various stimuli, such as the recognition of extracellular ATP by the P2X7 receptor. […] Based on the recent literature, we present evidence that supports the idea that the P2X7R/NLRP3 axis may be involved in the immune dysregulation caused by the SARS-CoV-2 infection.
32808940 The present study analyzes the importance of the inflammasome that involves the NLRP3 complex in the state of hypercytokinemia observed in patients with COVID-19, significantly increasing IL-1β, IL18, IL-6, and TNF. […] Studies show that colchicine, among other actions, inhibits the assembly of NLRP3 complex that is responsible for generating the active form of Caspase-1 that will convert Pro-IL-1β and Pro-IL-18 into their active forms.
32824985 The NLRP3 (NACHT, LRR and PYD domains-containing protein 3) inflammasome is implicated in a variety of human diseases including Alzheimer’s disease (AD), prion diseases, type 2 diabetes, and numerous infectious diseases. […] Of the three tested antibiotics, DDS was effective in the molecular regulation of NLRP3 inflammasome activators that are important in mild cognitive impairment (MCI), Parkinson’s disease (PD), and AD. […] The specific targeting of NLRP3 itself or up-/downstream factors of the NLRP3 inflammasome by DDS may be responsible for its observed preventive effects, functioning as a competitor.
32867310 NLRP3 inflammasome is a component of the innate immune response and different diseases, such as neurodegenerative diseases, are characterized by NLRP3 activation. […] This review aims to describe NLRP3 inflammasome and the consequences related to its activation following TBI. […] NLRP3, caspase-1, IL-1β, and IL-18 are significantly upregulated after TBI, therefore, the use of nonspecific, but mostly specific NLRP3 inhibitors is useful to ameliorate the damage post-TBI characterized by neuroinflammation. […] Moreover, NLRP3 and the molecules associated with its activation may be considered as biomarkers and predictive factors for other neurodegenerative diseases consequent to TBI. […] Complications such as continuous stimuli or viral infections, such as the SARS-CoV-2 infection, may worsen the prognosis of TBI, altering the immune response and increasing the neuroinflammatory processes related to NLRP3, whose activation occurs both in TBI and in SARS-CoV-2 infection. […] This review points out the role of NLRP3 in TBI and highlights the hypothesis that NLRP3 may be considered as a potential therapeutic target for the management of neuroinflammation in TBI.
32965010 NLRP3 (NOD-, LRR- and pyrin domain-containing protein 3) inflammasome has recently become an intriguing target of several chronic and viral diseases. […] Here, we argue that targeting NLRP3 inflammasome could be a strategy to prevent cardiovascular outcomes [fulminant myocarditis, heart failure, venous thromboembolism (VTE)] and acute respiratory distress syndrome (ARDS) in patients with SARS-CoV-2 infection. […] We discuss the rationale for NLRP3 targeting in clinical trials as an effective therapeutic strategy aimed to improve prognosis of COVID-19, analyzing the potential of two therapeutic options (tranilast and OLT1177) currently available in clinical practice.
32980515 NLRP3 inflammasome mediated release of interleukin-1β (IL-1β) has been implicated in various diseases, including COVID-19. […] In this study, rationally designed alkenyl sulfonylurea derivatives were identified as novel, potent and orally bioavailable NLRP3 inhibitors. […] Compound 7 was found to be potent (IL-1β IC50 = 35 nM; IL-18 IC50 = 33 nM) and selective NLRP3 inflammasome inhibitor with excellent pharmacokinetic profile having oral bioavailability of 99% in mice.
33014275 R-BHB activates anti-inflammatory GPR109A signaling and inhibits the NLRP3 inflammasome and histone deacetylases, while a ketogenic diet has been shown to protect mice from influenza virus infection through a protective γδ T cell response and by increasing electron transport chain gene expression to restore energy metabolism.
33032060 A long-term neurologic sequela arising from COVID-19 infection in multiple sclerosis (MS) patients could be related both to the increase of cytokines and the activation of NLRP3 inflammasome by the Sars-CoV2.
33041797 The shared genes included MMP13, NLRP3, TRIM21, GBP1, ADORA2A, PTAFR, TNF, MLNR, IL1B, NFKBIA, ADRB2, and IL6.
33079210 The orf8b protein of the coronavirus SARS-CoV, analogous to SARS-CoV-2, triggers the NLRP3 inflammasome in macrophages in vitro. […] We conducted staining for ASC (Apoptosis-associated Speck-like protein containing a Caspase recruitment domain), NLRP3 (NACHT, LRR, and PYD domains-containing protein 3), and cleaved caspase-1. […] These findings identify the presence of NLRP3 inflammasome aggregates in the lungs of fatal COVID-19 pneumonia thus providing the potential molecular link between viral infection and cytokine release syndrome.
33096114 The consequence of immunothrombosis include hypercoagulation, accelerating inflammation, fibrin deposition, migration of neutrophil extracellular traps (NETs) producing neutrophils into the alveolar apace, activation of the NLRP3 inflammazome, increased alveolar macrophage destruction and massive tissue damage by pyroptosis and necroptosis Therapeutic combinations aimed at ameliorating immunothrombosis and preventing the development of severe COVID-19 are discussed in detail.
33099890 NLRP3 inflammasome has been shown to play a key role in the pathogenesis of viral diseases. […] Curcumin regulates several molecules in the intracellular signal transduction pathways involved in inflammation, including IBB, NF-kBERK1,2, AP-1, TGF-β, TXNIP, STAT3, PPARγ, JAK2-STAT3, NLRP3, p38MAPK, Nrf2, Notch-1, AMPK, TLR-4 and MyD-88.
33110739 Anecdotal experiences have been reported with the use of the anti-IL-1 agent anakinra and the NLRP3 inflammasome inhibitor colchicine in this population.
33113418 We present reports where ASX is shown to prevent against oxidative damage and attenuate exacerbation of the inflammatory responses by regulating signaling pathways like NF-ĸB, NLRP3 and JAK/STAT.
33193349 the NLRP3 inflammasome activation and the release of pro-inflammatory cytokines from cells trough Gasdermin-pores commonly found in cell death by pyroptosis.
33203890 The IL-1 and NLRP3 inflammasome pathways are markedly less responsive to SARS-CoV-2, commensurate with a signature of diminished neutrophil and macrophage recruitment.
33231615 The NLRP3 inflammasome is a molecular platform that promotes inflammation via cleavage and activation of key inflammatory molecules including active caspase-1 (Casp1p20), IL-1β, and IL-18. […] Here we demonstrate that the NLRP3 inflammasome is activated in response to SARS-CoV-2 infection and is active in COVID-19 patients. […] Studying moderate and severe COVID-19 patients, we found active NLRP3 inflammasome in PBMCs and tissues of postmortem patients upon autopsy.
33254494 Siglec-5 and -14 are paired receptors with opposed actions on the NLRP3 inflammasome, which is critical in early viral clearance.
33269094 Excessive levels or activity of antimicrobial peptides, C-reactive protein, complement system, TLR/NF-κB, cGAS/STING/IFN 1,3 and AGEs/RAGE pathways, myeloid cells and NLRP3 inflammasome, declined levels of NK cells in innate immunity, thymus involution and decreased amount of naive T-cells in adaptive immunity, are biomarkers of aging and predisposition factors for cellular senescence and aging-related pathologies.
33328588 Elevated levels of extracellular ATP induced by SARS-CoV-2 infection may trigger hyperactivation of P2X7 receptors leading to NLRP3 inflammasome stimulation as a key mediator of neuroinvasion and consequent neuroinflammatory processes, as observed in psychiatric disorders and neurodegenerative diseases.
33375692 The NLRP3 inflammasome has received the most study and plays an important pathogenic role in a vast range of pathologies associated with inflammation-including atherosclerosis, myocardial infarction, the complications of diabetes, neurological and autoimmune disorders, dry macular degeneration, gout, and the cytokine storm phase of COVID-19.
33416933 NLRP3 inflammasome has been shown to play a key role in the pathogenesis of viral diseases. […] The possible role of NLRP3 inflammasome inhibitors in the treatment of COVID-19 has been considered. […] Studies indicate that one of the possible anti-inflammatory mechanisms of chloroquine and hydroxychloroquine is inhibition of the activity of NLRP3 inflammasome.
33426541 Both lead to the activation of inflammasome NLRP3, which stimulates transcription factor NFκB and the production of inflammatory cytokines.
33479353 We also detected strong downregulation of the NLRP3 gene, critical for maintenance of homeostasis against pathogenic infections, possibly leading to bacterial infection complications.
33499042 We will briefly touch upon the recently discovered role of NLRP3 as a transcriptional regulator, which suggests that transcriptional regulation is, after all, not such an unusual feature for NLR proteins.
33509217 Activation or inhibition of the NLRP3 inflammasome is affected by regulators such as TXNIP, SIRT1 and NRF2. […] Quercetin suppresses the NLRP3 inflammasome by affecting these regulators.
33509749 The binding of MOL000522, MOL004989, and MOL003330 with MAPK1; MOL001495 and MOL001494 with NLRP3; MOL004908, MOL004863 and MOL004806 with HSP90AA1; MOL001749 with TLR9; and MOL001495 with AKT1 all had total scores exceeding 9.0. capsule contains multiple effective ingredients to improve clinical cure rate of COVID-19, and its therapeutic effect is mediated by multiple protein targets, signal pathways and biological functions.
33531826 Within the nucleic acid-sensing pathways, SARS-CoV-2 infection and evasion mechanisms trigger the activation of NOD-signaling and NLRP3 pathways leading to the production of inflammatory cytokines, IL-1β and IL-6, while muting or blocking cGAS-STING and interferon type I and III pathways, resulting in decreased production of antiviral interferons and delayed innate response.
33537958 The functional modules and pathway enrichment analysis of the association network clearly show that the application of probiotics could have therapeutic effects on ACE2-mediated virus entry, activation of the systemic immune response, nlrp3-mediated immunomodulatory pathways, immune cell migration resulting in lung tissue damage and cardiovascular difficulties, and altered glucose/lipid metabolic pathways in the disease prognosis.
33549591 In addition to these intracellular and mitochondrial processes, we discuss how the SDOH-exposome can influence the balance between metabolism and regulation of immune responsiveness involving the two main molecular drivers of inflammation, the NLRP3 inflammasome and NF-κB induction.
33553222 In addition, high expression of CD147, an alternative receptor, and activation of the NLRP3 inflammasome may also contribute to atherosclerosis in the context of COVID-19.