Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

The Multifaceted Role and Regulation of Nlrp3 Inflammasome in Colitis-Associated Colo-Rectal Cancer: A Systematic Review.

ABSTRACT: Colitis-associated colo-rectal cancer remains the leading cause of mortality in inflammatory bowel diseases, with inflammation remaining one of the bridging points between the two pathologies. The NLRP3 inflammasome complex plays an important role in innate immunity; however, its misregulation can be responsible for the apparition of various pathologies such as ulcerative colitis. Our review focuses on the potential pathways of upregulation or downregulation of the NLRP3 complex, in addition to evaluating its role in the current clinical setting. Eighteen studies highlighted the potential pathways of NLRP3 complex regulation as well as its role in the metastatic process in colo-rectal cancer, with promising results. Further research is, however, needed in order to validate the results in a clinical setting.

SUBMITTER: Zaharie R

PROVIDER: S-EPMC9959003 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

The Multifaceted Role and Regulation of Nlrp3 Inflammasome in Colitis-Associated Colo-Rectal Cancer: A Systematic Review.

Zaharie Roxana R Valean Dan D Popa Calin C Fetti Alin A Zdrehus Claudiu C Puia Aida A Usatiuc Lia L Schlanger Diana D Zaharie Florin F

International journal of molecular sciences 20230209 4

Colitis-associated colo-rectal cancer remains the leading cause of mortality in inflammatory bowel diseases, with inflammation remaining one of the bridging points between the two pathologies. The NLRP3 inflammasome complex plays an important role in innate immunity; however, its misregulation can be responsible for the apparition of various pathologies such as ulcerative colitis. Our review focuses on the potential pathways of upregulation or downregulation of the NLRP3 complex, in addition to ...[more]

PMID: 36834883

Similar Datasets

NLRP3 inflammasome has a protective effect against oxazolone-induced colitis: a possible role in ulcerative colitis.

Project description:The inflammasomes induce maturation of pro-interleukin-1β (IL-1β) and pro-IL-18. We investigated roles of the NLRP3 inflammasome in the pathogenesis of ulcerative colitis (UC). After induction of oxazolone-induced colitis, a mouse UC model, colonic tissues were assayed for inflammatory mediators. Histological studies were performed on inflamed colonic tissue from mice and UC patients. Histological severity of murine colitis peaked on day 1, accompanied by an increase in the expression of Th2 cytokines including IL-4 and IL-13. Oxazolone treatment stimulated maturation of pro-caspase-1 and pro-IL-1β, while it reduced IL-18 expression. Either exogenous IL-1β or IL-18 ameliorated the colitis with or without reduction in Th2 cytokine expression, respectively. Induction of colitis decreased MUC2 expression, which was reversed by administration of IL-18, but not IL-1β. Compared to wild-type mice, NLRP3-/- mice exhibited higher sensitivity to oxazolone treatment with enhancement of Th2 cytokine expression and reduction of mature IL-1β and IL-18 production; this phenotype was rescued by exogenous IL-1β or IL-18. Immunofluorescent studies revealed positive correlation of NLRP3 expression with disease severity in UC patients, and localization of the inflammasome-associated molecules in macrophages. The NLRP3 inflammasome-derived IL-1β and IL-18 may play a protective role against UC through different mechanisms.

| S-EPMC5155456 | biostudies-literature

Oroxylin A inhibits colitis by inactivating NLRP3 inflammasome.

Project description:NLRP3 inflammasome is a novel therapeutic target for inflammatory bowel disease (IBD). The aim of this study was to investigate the anti-inflammatory effect of a bioactive flavonoid-oroxylin A on the treatment of dextran sulfate sodium (DSS)-induced murine colitis via targeting NLRP3 inflammasome. In this study, we found that oroxylin A attenuated experimental colitis in mice, including loss of body weights, shortening of the colon lengths and infiltration of inflammatory cells. The production of IL-1β, IL-6 and TNF-α in colon was also markedly reduced by oroxylin A. Moreover, oroxylin A significantly decreased the expression of NLRP3 in intestinal mucosal tissue. In addition, NLRP3-/- mice were observably protected from DSS-induced acute colitis, and oroxylin A treatment had no effects on attenuating inflammation in NLRP3-/- mice. Further study found that the activation of NLRP3 inflammasome was dose-dependently inhibited by oroxylin A in both THP-Ms and BMDMs, followed by decrease in the cleavage of caspase-1 and secretion of IL-1β. This inhibitory effect of oroxylin A was due to restraint of the NLRP3 protein expression and the inflammasome formation in macrophages. Furthermore, the reduction of NLRP3 protein expression by oroxylin A was dependent on the inhibition of NF-κB p65 expression and nuclear translocation. Besides, oroxylin A directly suppressed the ASC speck formation and the inflammasome assembly which in turn restrained the activation of NLRP3 inflammasome. Our findings demonstrated that oroxylin A inhibited NLRP3 inflammasome activation and could potentially be used for the treatment of IBD.

| S-EPMC5601702 | biostudies-literature

Regulation of NLRP3 Inflammasome by Phosphorylation.

Project description:The cytosolic pattern recognition receptor (PRR) NOD-like receptor family, pyrin domain containing 3 (NLRP3) senses a wide range of pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs). Upon activation, NLRP3 triggers the assembly of inflammasome via the self-oligomerization and the recruitment of apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC) and pro-caspase-1, facilitating the robust immune responses including the secretion of proinflammatory cytokines and pyroptosis. The NLRP3 inflammasome must be well orchestrated to prevent the aberrant activations under physiological and pathological conditions, because uncontrolled activation of NLRP3 inflammasome is one of the major causes of a variety of autoimmune diseases and metabolic disorders. Therefore, understanding the molecular mechanisms for controlling NLRP3 inflammasome activation may provide novel strategies for the treatment of NLRP3-related diseases. Although NLRP3 inflammasome can be regulated at the transcriptional level, the post-translational modification (PTM) of NLRP3 as well as other inflammasome components has also been showed to be critical for the regulation of its activation. Several kinases and phosphatases have been shown to control NLRP3 inflammasome activation in response to either exogenous pathogen infections or endogenous molecules, such as bile acids. In this review, we summarize our current knowledge of phosphorylation patterns and their functional role in the regulation of NLRP3 inflammasome, and suggest interesting areas for future research.

| S-EPMC6186804 | biostudies-other

ABRO1 promotes NLRP3 inflammasome activation through regulation of NLRP3 deubiquitination

Project description:Deubiquitination of NLRP3 has been suggested to contribute to inflammasome activation, but the roles and molecular mechanisms are still unclear. We here demonstrate that ABRO1, a subunit of the BRISC deubiquitinase complex, is necessary for optimal NLRP3-ASC complex formation, ASC oligomerization, caspase-1 activation, and IL-1? and IL-18 production upon treatment with NLRP3 ligands after the priming step, indicating that efficient NLRP3 activation requires ABRO1. Moreover, we report that ABRO1 deficiency results in a remarkable attenuation in the syndrome severity of NLRP3-associated inflammatory diseases, including MSU- and Alum-induced peritonitis and LPS-induced sepsis in mice. Mechanistic studies reveal that LPS priming induces ABRO1 binding to NLRP3 in an S194 phosphorylation-dependent manner, subsequently recruiting the BRISC to remove K63-linked ubiquitin chains of NLRP3 upon stimulation with activators. Furthermore, deficiency of BRCC3, the catalytically active component of BRISC, displays similar phenotypes to ABRO1 knockout mice. Our ?ndings reveal an ABRO1-mediated regulatory signaling system that controls activation of the NLRP3 in?ammasome and provide novel potential targets for treating NLRP3-associated inflammatory diseases.

| S-SCDT-EMBOJ-2018-100376 | biostudies-other

NLRP3 inflammasome plays a key role in the regulation of intestinal homeostasis.

Project description:Attenuated innate immune responses to the intestinal microbiota have been linked to the pathogenesis of Crohn's disease (CD). Recent genetic studies have revealed that hypofunctional mutations of NLRP3, a member of the NOD-like receptor (NLR) superfamily, are associated with an increased risk of developing CD. NLRP3 is a key component of the inflammasome, an intracellular danger sensor of the innate immune system. When activated, the inflammasome triggers caspase-1-dependent processing of inflammatory mediators, such as IL-1? and IL-18.In the current study we sought to assess the role of the NLRP3 inflammasome in the maintenance of intestinal homeostasis through its regulation of innate protective processes. To investigate this role, Nlrp3(-/-) and wildtype mice were assessed in the dextran sulfate sodium and 2,4,6-trinitrobenzenesulfonic acid models of experimental colitis.Nlrp3(-/-) mice were found to be more susceptible to experimental colitis, an observation that was associated with reduced IL-1?, reduced antiinflammatory cytokine IL-10, and reduced protective growth factor TGF-?. Macrophages isolated from Nlrp3(-/-) mice failed to respond to bacterial muramyl dipeptide. Furthermore, Nlrp3-deficient neutrophils exhibited reduced chemotaxis and enhanced spontaneous apoptosis, but no change in oxidative burst. Lastly, Nlrp3(-/-) mice displayed altered colonic ?-defensin expression, reduced colonic antimicrobial secretions, and a unique intestinal microbiota.Our data confirm an essential role for the NLRP3 inflammasome in the regulation of intestinal homeostasis and provide biological insight into disease mechanisms associated with increased risk of CD in individuals with NLRP3 mutations.

| S-EPMC3026862 | biostudies-literature

Contradictory Effects of NLRP3 Inflammasome Regulatory Mechanisms in Colitis.

Project description:The inflammasome is an intracellular molecular complex, which is mainly involved in innate immunity. Inflammasomes are formed in response to danger signals, associated with infection and injury, and mainly regulate the secretion of interleukin-1β and interleukin-18. Inflammasome dysregulation is known to be associated with various diseases and conditions, and its regulatory mechanisms have become of great interest in recent years. In the colon, inflammasomes have been reported to be associated with autophagy and the microbiota, and their dysregulation contributes to colitis and. However, the detailed role of inflammasomes in inflammatory bowel disease is still under debate because the mechanisms that regulate the inflammasome are complex and the inflammasome components and cytokines show seemingly contradictory multiple effects. Herein, we comprehensively review the literature on inflammasome functioning in the colon and describe the complex interactions of the NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome components with inflammatory cytokines, autophagy, and the microbiota in experimental colitis models and patients with inflammatory bowel disease.

| S-EPMC7662299 | biostudies-literature

ABRO1 promotes NLRP3 inflammasome activation through regulation of NLRP3 deubiquitination.

Project description:Deubiquitination of NLRP3 has been suggested to contribute to inflammasome activation, but the roles and molecular mechanisms are still unclear. We here demonstrate that ABRO1, a subunit of the BRISC deubiquitinase complex, is necessary for optimal NLRP3-ASC complex formation, ASC oligomerization, caspase-1 activation, and IL-1β and IL-18 production upon treatment with NLRP3 ligands after the priming step, indicating that efficient NLRP3 activation requires ABRO1. Moreover, we report that ABRO1 deficiency results in a remarkable attenuation in the syndrome severity of NLRP3-associated inflammatory diseases, including MSU- and Alum-induced peritonitis and LPS-induced sepsis in mice. Mechanistic studies reveal that LPS priming induces ABRO1 binding to NLRP3 in an S194 phosphorylation-dependent manner, subsequently recruiting the BRISC to remove K63-linked ubiquitin chains of NLRP3 upon stimulation with activators. Furthermore, deficiency of BRCC3, the catalytically active component of BRISC, displays similar phenotypes to ABRO1 knockout mice. Our findings reveal an ABRO1-mediated regulatory signaling system that controls activation of the NLRP3 inflammasome and provide novel potential targets for treating NLRP3-associated inflammatory diseases.

| S-EPMC6418445 | biostudies-literature

Role of NLRP3 Inflammasome in Rheumatoid Arthritis.

Project description:Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by multi-articular, symmetrical and invasive arthritis resulting from immune system abnormalities involving T and B lymphocytes. Although significant progress has been made in the understanding of RA pathogenesis, the underlying mechanisms are not fully understood. Recent studies suggest that NLRP3 inflammasome, a regulator of inflammation, might play an important role in the development of RA. There have been increasing clinical and pre-clinical evidence showing the treatment of NLRP3/IL-1β in inflammatory diseases. To provide a foundation for the development of therapeutic strategies, we will briefly summarize the roles of NLRP3 inflammasome in RA and explore its potential clinical treatment.

| S-EPMC9271572 | biostudies-literature

Role of the NLRP3 inflammasome in cancer.

Project description:Inflammasomes are large intracellular multi-protein signalling complexes that are formed in the cytosolic compartment as an inflammatory immune response to endogenous danger signals. The formation of the inflammasome enables activation of an inflammatory protease caspase-1, pyroptosis initiation with the subsequent cleaving of the pro-inflammatory cytokines interleukin (IL)-1β and proIL-18 to produce active forms. The inflammasome complex consists of a Nod-like receptor (NLR), the adapter apoptosis-associated speck-like (ASC) protein, and Caspase-1. Dysregulation of NLRP3 inflammasome activation is involved tumor pathogenesis, although its role in cancer development and progression remains controversial due to the inconsistent findings described. In this review, we summarize the current knowledge on the contribution of the NLRP3 inflammasome on potential cancer promotion and therapy.

| S-EPMC6240225 | biostudies-literature

SUMO-mediated regulation of NLRP3 modulates inflammasome activity.

Project description:The NLRP3 inflammasome responds to infection and tissue damage, and rapidly escalates the intensity of inflammation by activating interleukin (IL)-1β, IL-18 and cell death by pyroptosis. How the NLRP3 inflammasome is negatively regulated is poorly understood. Here we show that NLRP3 inflammasome activation is suppressed by sumoylation. NLRP3 is sumoylated by the SUMO E3-ligase MAPL, and stimulation-dependent NLRP3 desumoylation by the SUMO-specific proteases SENP6 and SENP7 promotes NLRP3 activation. Defective NLRP3 sumoylation, either by NLRP3 mutation of SUMO acceptor lysines or depletion of MAPL, results in enhanced caspase-1 activation and IL-1β release. Conversely, depletion of SENP7 suppresses NLRP3-dependent ASC oligomerisation, caspase-1 activation and IL-1β release. These data indicate that sumoylation of NLRP3 restrains inflammasome activation, and identify SUMO proteases as potential drug targets for the treatment of inflammatory diseases.

| S-EPMC6070540 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data