Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA253986 | ENA |
REPOSITORIES: ENA
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Project description:Inflammasome, activated by pathogen-derived and host-derived danger signals, constitutes a multimolecular signaling complex that serves as a platform for caspase-1 (CASP1) activation and interleukin-1beta (IL1B) maturation. The activation of NLRP3 inflammasome requires two-step signals. The first “priming” signal (Signal 1) enhances gene expression of inflammasome components. The second “activation” signal (Signal 2) promotes the assembly of inflammasome components. Deregulated activation of NLRP3 inflammasome contributes to the pathological processes of Alzheimer’s disease (AD) and multiple sclerosis (MS). However, at present, the precise mechanism regulating NLRP3 inflammasome activation and deactivation remains largely unknown. By genome-wide gene expression profiling, we studied the molecular network of NLRP3 inflammasome activation-responsive genes in a human monocyte cell line THP-1 sequentially given two-step signals. We identified the set of 83 NLRP3 inflammasome activation-responsive genes. Among them, we found the NR4A nuclear receptor family NR4A1, NR4A2, and NR4A3, the EGR family EGR1, EGR2, and EGR3, the IkappaB family NFKBIZ, NFKBID, and NFKBIA as a key group of the genes that possibly constitute a negative feedback loop for shutting down inflammation following NLRP3 inflammasome activation. By molecular network analysis, we identified a complex network of NLRP3 inflammasome activation-responsive genes involved in cellular development and death, and immune and inflammatory responses, where transcription factors AP-1, NR4A, and EGR serve as a hub. Thus, NLRP3 inflammasome activation-responsive genes constitute the molecular network composed of a set of negative feedback regulators for prompt resolution of inflammation. To load the Signal 1 (S1), THP-1 cells were incubated for 3 hours in the culture medium with or without inclusion of 0.2 microgram/ml lipopolysaccharide (LPS). To load the Signal 2 (S2), they were incubated further for 2 hours in the culture medium with inclusion of 10 microM nigericin sodium salt dissolved in ethanol or the equal v/v% concentration of ethanol (vehicle), followed by processing for microarray analysis on Human Gene 1.0 ST Array (Affymetrix).
2014-07-01 | E-GEOD-58959 | biostudies-arrayexpress
Project description:Inflammasome, activated by pathogen-derived and host-derived danger signals, constitutes a multimolecular signaling complex that serves as a platform for caspase-1 (CASP1) activation and interleukin-1beta (IL1B) maturation. The activation of NLRP3 inflammasome requires two-step signals. The first “priming” signal (Signal 1) enhances gene expression of inflammasome components. The second “activation” signal (Signal 2) promotes the assembly of inflammasome components. Deregulated activation of NLRP3 inflammasome contributes to the pathological processes of Alzheimer’s disease (AD) and multiple sclerosis (MS). However, at present, the precise mechanism regulating NLRP3 inflammasome activation and deactivation remains largely unknown. By genome-wide gene expression profiling, we studied the molecular network of NLRP3 inflammasome activation-responsive genes in a human monocyte cell line THP-1 sequentially given two-step signals. We identified the set of 83 NLRP3 inflammasome activation-responsive genes. Among them, we found the NR4A nuclear receptor family NR4A1, NR4A2, and NR4A3, the EGR family EGR1, EGR2, and EGR3, the IkappaB family NFKBIZ, NFKBID, and NFKBIA as a key group of the genes that possibly constitute a negative feedback loop for shutting down inflammation following NLRP3 inflammasome activation. By molecular network analysis, we identified a complex network of NLRP3 inflammasome activation-responsive genes involved in cellular development and death, and immune and inflammatory responses, where transcription factors AP-1, NR4A, and EGR serve as a hub. Thus, NLRP3 inflammasome activation-responsive genes constitute the molecular network composed of a set of negative feedback regulators for prompt resolution of inflammation.
2014-07-01 | GSE58959 | GEO
Project description:Viral antigens can activate phagocytes inducing inflammation but the mechanisms are barely explored. This study aimed to investigate the capability of viral oligomeric proteins of different structure to induce inflammatory response in macrophages. Human THP-1 cell line was used to prepare macrophages which were treated with filamentous nucleocapsid-like particles (NLPs) of paramyxoviruses and spherical virus-like particles (VLPs) of human polyomaviruses. The effects of viral proteins on cell viability, pro-inflammatory cytokines’ production and formation of NLRP3 inflammasome components, ASC specks, were investigated. Filamentous NLPs did not induce inflammation markers while spherical VLPs mediated inflammatory response followed by NLRP3 inflammasome activation. Inhibitors of cathepsins and K+ efflux decreased IL-1β levels and cell death indicating a complex inflammasome activation process. Similar activation pattern was observed in primary human macrophages treated with VLPs. Single cell RNAseq analysis of THP-1 cells revealed several cell activation states characterized by high expression of inflammation-related genes. This study provides new insights into interaction of viral proteins with innate immune cells and suggests that structural properties of oligomeric proteins may define cell activation pathways.
2022-02-21 | GSE190666 | GEO
Project description:Inflammasomes are multi-protein complexes that control the production of pro-inflammatory cytokines such as IL-1beta. Inflammasomes play an important role in the control of immunity to tumors and infections, and also in autoimmune diseases, but the mechanisms controlling the activation of human inflammasomes are largely unknown. We found that human activated CD4+CD45RO+ memory T-cells specifically suppress P2X7R-mediated NLRP3 inflammasome activation, without affecting P2X7R-independent NLRP3 or NLRP1 inflammasome activation. The concomitant increase in pro-IL-1β production induced by activated memory T-cells concealed this effect. Priming with IFNβ decreased pro-IL-1β production in addition to NLRP3 inflammasome inhibition and thus unmasked the inhibitory effect on NLRP3 inflammasome activation. IFNβ did not suppress NLRP3 inflammasome activation by acting directly on monocytes. The inhibition of pro-IL-1β production and suppression of NLRP3 inflammasome activation by IFNβ-primed human CD4+CD45RO+ memory T-cells is partly mediated by soluble FasL and is associated with down-regulated P2X7R mRNA expression and reduced response to ATP in monocytes. CD4+CD45RO+ memory T-cells from multiple sclerosis (MS) patients showed a reduced ability to suppress NLRP3 inflammasome activation, however their suppressive ability was recovered following in vivo treatment with IFNβ. Thus, our data demonstrate that human P2X7R-mediated NLRP3 inflammasome activation is regulated by activated CD4+CD45RO+ memory T cells, and provide new information on the mechanisms mediating the therapeutic effects of IFNβ in MS. Memory T-cells were cultured in the presence of monocytes with and without Interferon-beta, resorted and expression profile was determined
2012-12-01 | E-GEOD-35601 | biostudies-arrayexpress
Project description:The immune system may respond to engineered nanomaterials (ENM) through inflammatory reactions. The NLRP3 inflammasome responds to a wide range of ENM, and its activation is associated with various inflammatory diseases. The objective of the study was to compare the effects of gold ENM of different shapes on NLRP3 inflammasome activation and related signalling pathways. Differentiated THP-1 cells (wildtype, ASC- or NLRP3-deficient), were exposed to PEGylated gold nanorods, nanostars, and nanospheres. Exposed cells were subjected to gene expression analysis. Nanorods, but not nanostars or nanospheres, showed NLRP3 inflammasome activation. ASC- or NLRP3-deficient cells did not show this effect. Gold nanorod-induced NLRP3 inflammasome activation was accompanied by downregulated sterol/cholesterol biosynthesis, oxidative phosphorylation, and purinergic receptor signalling. In conclusion, the shape and surface chemistry of gold nanoparticles determine NLRP3 inflammasome activation.
2023-05-29 | GSE233641 | GEO
Project description:The NLRP3 inflammasome plays a central role in antimicrobial defense as well as in the context of sterile inflammatory conditions. NLRP3 activity is governed by two independent signals: The first signal primes NLRP3, rendering it responsive to the second signal, which then triggers inflammasome formation. Our understanding of how NLRP3 priming contributes to inflammasome activation remains limited. Here we show that IKKβ, a kinase activated during priming, induces recruitment of NLRP3 to phosphatidylinositol-4-phosphate (PI4P), a lipid enriched on the trans-Golgi network. Intriguingly, NEK7, a mitotic spindle kinase that had previously been thought to be indispensable for NLRP3 activation, was redundant for inflammasome formation when IKKβ recruited NLRP3 to PI4P. Studying iPSC-derived human macrophages revealed that the IKKβ-mediated NEK7-independent pathway constitutes the predominant NLRP3 priming mechanism in human myeloid cells. Our results suggest that PI4P binding represents a new type of "primed" state into which NLRP3 is brought by IKKβ activity.
2022-11-17 | PXD035302 | Pride
Project description:Inflammasome activation in macrophages induces the release of EVs, however, the effect of these inflammasome-induced EVs on recipient cells is poorly characterized. To characterize the effect EVs released upon LPS + nigericin stimulation, we performed 3' sequencing on the recipient cells (NLRP3 KO THP-1 macrophages and NLRP3 KO THP-1 macrophages that have been reconstituted with NLRP3 to resemble the WT). As controls, RNA isolated from EVs themselves or LPS- or nigericin-treated cells were subjected to 3' sequencing.
2021-07-26 | GSE180707 | GEO
Project description:This study aims to characterize the proteomic profile of extracellular vesicles (EVs) derived from human macrophages activated via the NLRP3 inflammasome pathway. THP-1 cells were stimulated with LPS and Nigericin to induce NLRP3 activation, followed by EV isolation. The protein contents of EVs were analyzed using LC-MS/MS. This dataset includes both raw MS data and processed identification files to support further investigation into inflammation-related EV signaling.
2026-01-14 | PXD064778 | JPOST Repository
Project description:<p>Shi Wei Ru Xiang pill (SWR) is commonly utilized in Tibetan medicine as a therapeutic intervention for 'Huang-shui disease' and has been clinically validated as an effective treatment for acute gouty arthritis (AGA). Nevertheless, the underlying mechanisms of action and the active components of SWR in combating AGA remain unclear. In this study, the effects of SWR and its active components on AGA and NLRP3 inflammasome activation were investigated in monosodium urate (MSU)-induced AGA rats and lipopolysaccharide/nigericin-induced THP-1 cells. The chemical profile of SWR was characterized using UPLC-Q-Exactive Orbitrap MS. The results indicated that SWR effectively suppressed pyroptosis, caspase-1 activity, and IL-1β production in THP-1 cells. Furthermore, SWR significantly suppressed NLRP3 inflammasome activation and attenuated ankle swelling in a rat AGA model. Specifically, SWR affected the priming and assembly phases to inhibit NLRP3 inflammasome activation. Surprisingly, SWR showed good liver and renal protective effects in AGA rats. A total of 58 compounds were identified in SWR by UPLC-MS analysis. Further pharmacological studies demonstrated that the phenolic compounds serve as active compounds responsible for the inhibition of inflammasome activation, including dehydrocostus lactone, gallic acid, 4-hydroxybenzoic acid. This is the first study to comprehensively elucidate the therapeutic effects and underlying mechanisms of SWR against AGA by inhibiting NLRP3 inflammasome activation. This study strongly indicated that SWR could serve as a promising anti-inflammatory medicine with an acceptable safety profile for the treatment of AGA and other inflammatory disorders linked to NLRP3 inflammasome activation</p>
2025-06-20 | MTBLS12617 | MetaboLights
Project description:The terminal stage of the complement activation pathways, the membrane attack complex (MAC), is upregulated in diabetic and rheumatoid arthritis patients, contributing pathologically by increasing inflammation. Previous research has highlighted that a sublytic dose of MAC can initiate NLRP3 inflammasome activation via calcium influx and loss of mitochondrial membrane potential. Here, we show that sublytic concentrations of MAC mediate a previously undescribed perturbation in cellular energy metabolism in human monocyte-derived macrophages, by phenotypic skewing towards glycolysis and upregulation of glycolysis-promoting genes. Sublytic MAC concentrations drive mitochondrial dysfunction, characterised by a fragmented mitochondrial morphology, loss of maximal respiratory response, depleted mitochondrial membrane potential as well as increased mitochondrial reactive oxygen species production. The consequences of these alterations in glycolytic metabolism and mitochondrial dysfunction lead to NLRP3 inflammasome activation, driving gasdermin D formation and IL-18 release. This novel link between sublytic MAC and immunometabolism, with direct consequences for downstream inflammatory processes, is important for development of novel therapeutics for areas where MAC may mediate disease.
2023-03-11 | PXD027316 | Pride