Splenic and adipose B cells from wild-type and Nlrp3-/- mice
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE137144 | GEO | 2022/08/29
REPOSITORIES: GEO
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Project description:Splenic and adipose B cells from wild-type and Nlrp3-/- mice
| PRJNA564630 | ENA
Project description:Aging is the major risk factor for cardiovascular and many other chronic diseases. During this natural process, many alterations occur in the organism which are associated with progressive impairment of several metabolic pathways related to body composition, insulin resistance, mitochondrial and autophagy dysfunction and inflammation. Recently, the role of NLRP3 inflammasome has been studied in cardiovascular diseases showing its implication in the pathological progression of atherosclerosis, heart failure, and hypertension. However, the role of the NLRP3 inflammasome in cardiac aging has been less well studied. Herein, we investigate the molecular mechanisms by which NLRP3 inhibition may attenuate cardiac aging. Ablation of NLRP3 inflammasome increased lifespan and protected mice from age-related increased insulin sensitivity, reduced IGF-1 and leptin/adiponectin ratio levels, and reduced cardiac damage with protection of the prolongation of age–dependent PR interval, which is associated with atrial fibrillation by cardiovascular aging. Furthermore, old NLRP3 KO mice showed an inhibition of PI3K/AKT/mTOR pathway and autophagy improvement compared with old wild type mice and preserved Nampt-mediated NAD+ levels with increased SIRT1 protein expression. These findings suggest that suppression of NLRP3 prevented many age-associated changes in the heart and preserved cardiac function of aged mice.
2019-10-01 | GSE124483 | GEO
Project description:Analysis of gene expressions in mouse splenic dendritic cells (DCs). DCs were purified into two subsets, CD8-positive and -negative ones. DCs were expanded in vivo by injecting Flt3L-producing tumors into the backs of C57BL/6 mice.
2009-02-01 | GSE13250 | GEO
Project description:Objective: Adipose tissue plays a key role in obesity related metabolic dysfunction. MicroRNA (miRNA) are gene regulatory molecules involved in inter-cellular and inter-organ communication. We hypothesised that miRNA levels in adipose tissue would change after gastric bypass surgery and that this would provide insights into their role in obesity-induced metabolic dysregulation. Methods: miRNA-profiling (Affymetrix_Gene-Chip_miRNA2.0_Arrays) of omental and subcutaneous adipose (n=15 females) before, and after, gastric bypass surgery. Results: One omental, and thirteen subcutaneous adipose miRNAs were significantly, differentially expressed after gastric bypass, including down-regulation of miR-223-3p and its antisense relative, miR-223-5p, in both adipose tissues. mRNA levels of miR-223-3p targets NLRP3 and GLUT4 were increased and decreased respectively following gastric bypass in both adipose tissues. Significantly more NLRP3 protein was observed in omental adipose after gastric bypass (P=0.02). Significant hypomethlyation of NLRP3 and hypermethylation of miR-223 was observed in both adipose tissues after gastric bypass. In subcutaneous adipose significant correlations were observed between both miR-223-3p and miR-223-5p and glucose, and between NLRP3 mRNA and protein levels and blood lipids. Conclusions: This is the first report detailing genome-wide miRNA-profiling of omental adipose before and after gastric bypass, and further highlights a link between miR-223-3p and the NLRP3 inflammasome in obesity.
2019-12-16 | E-MTAB-8594 | biostudies-arrayexpress
Project description:Analysis of gene expressions in mouse splenic dendritic cells (DCs). DCs were purified into two subsets, CD8-positive and -negative ones. DCs were expanded in vivo by injecting Flt3L-producing tumors into the backs of C57BL/6 mice. To expand DCs in vivo, Flt3L-producing B16 melanoma cells were injected to the backs of mice. Then, 10-12 days later, splenic DCs were enriched by MACS and purified into CD3-B220-CD8a+CD11c+ and CD3-B220-CD8a-CD11c+ cells by FACS cell sorter.
2009-02-01 | E-GEOD-13250 | biostudies-arrayexpress
Project description:Immune response genes are disproportionately polymorphic in humans and mice, with heterogeneity amongst loci driving strain specific host defense responses. The inadvertent retention of polymorphic loci can confound results, lead to false conclusions, and delay scientific progress. By combining RNAseq and variant calling analyses, we identify a substantial region of 129S genome, including the highly polymorphic Nlrp1 locus proximal to Nlrp3, in one of the most commonly used mouse models of NLRP3 deficiency. We show that 129S NLRP1 can be tolerated at higher expression levels at steady-state, however this sensitizes Nlrp3-/- mice to NLRP1 inflammasome activation. Furthermore, the presence of 129S genome leads to altered gene and protein regulation across multiple cell-types, including of the key tissue-resident macrophage marker, TIM4. In order to resolve NLRP3 dependent phenotypes we validate a conditional Nlrp3 allele enabling temporal and cell-type specific control of NLRP3 deletion. Our study provides an accessible strategy to identify functionally relevant SNPs and assess genomic contamination in transgenic mice, to allow for unambiguous attribution of phenotypes to the target gene.
2024-01-23 | E-MTAB-13601 | biostudies-arrayexpress
Project description:CD8+ T cells derived from mice with intact NLRP3 signaling in the tumor microenvironment showed an increased expression of coinhibitory receptors PD-1, TIM-3, 2B4 and LAG-3 compared to CD8+ T cells from PancOVA-bearing Nlrp3-/- mice, indicating that NLRP3 inflammasome activation in the tumor microenvironment mediates IL-18 receptor signaling-induced T cell exhaustion. RNAseq was used to characterised molecular pathways involved in T cell plasticity in the presence and absence of intratumoral NLRP3.
2022-04-14 | GSE200570 | GEO
Project description:The NLRP3 inflammasome is a multi-protein complex that triggers the activation of the inflammatory protein caspase-1 and the maturation of the cytokine IL-1 in response to microbes and other danger signals in host cells. Here, we sought a deeper understanding of how the NLRP3 inflammasome is regulated. We found that inflammasome activation induced the Src family kinase Lyn to phosphorylate NLRP3 at Tyr918, and that this phosphorylation of NLRP3 correlated with a subsequent increase in its ubiquitination, which facilitated its proteasome-mediated degradation. NLRP3 tyrosine phosphorylation and ubiquitination was abrogated in Lyn-deficient macrophages, which produced increased amounts of IL-1. Furthermore, mice lacking Lyn were highly susceptible to LPS-induced septic shock in an NLRP3-dependent manner. Our data demonstrate that Lyn-mediated tyrosine phosphorylation of NLRP3 is a prerequisite for its ubiquitination, thus dampening NLRP3 inflammasome activity.
2022-05-19 | PXD028582 | Pride
Project description:Brown adipose tissue (BAT), a crucial heat-generating organ, regulate whole-body energy metabolism by mediating thermogenesis. BAT inflammation is implicated in the pathogenesis of mitochondrial dysfunction and impaired thermogenesis. However, the link between BAT inflammation and systematic metabolism remains unclear. Herein, we sought whether BAT inflammation regulates systematic metabolism and thermogenesis. By using mice with BAT deficiency of thioredoxin-2 (TRX2), a protein that scavenges mitochondrial reactive oxygen species (ROS), we evaluated the impact of BAT inflammation on metabolism and thermogenesis and its underlying mechanism. Our results describe that BAT-specific TRX2 ablation improves systematic metabolic performance via enhancing lipid uptake, which protects mice from diet-induced obesity, hypertriglyceridemia, and insulin resistance. TRX2 deficiency impairs adaptive thermogenesis by suppressing fatty acid oxidation. Mechanistically, loss of TRX2 induces excessive mitochondrial ROS, mitochondrial integrity disruption, and cytosolic release of mitochondrial DNA, which in turn activate aberrant innate immune responses in BAT, including the cGAS-STING and the NLRP3 inflammasome pathways. We identify NLRP3 as a key converging point, as its inhibition reverses both the thermogenesis defect and the metabolic benefits seen under nutrient overload in BAT-specific Trx2-deficient mice. In conclusion, we identify TRX2 as a critical hub integrating oxidative stress, inflammation, and lipid metabolism in BAT; uncovering an adaptive mechanism underlying the link between BAT inflammation and systematic metabolism.
2022-05-04 | GSE191009 | GEO
Project description:This experiment was performed to analyze the contribution of NLRP3 inflammasome activation to age-related changes in hippocampal RNA. The hypothesis was that decreased inflammasome activation would reduce hippocampal inflammation. Results indicate that inflammasome knockout animals are protected from age-related changes in hippocampal gene expression Gene expression profiles of young (1 month) and old (21-23 month) wild type, CIAS -/- and ASC -/- mouse hippocampal tissue were compared. Total mRNA was extracted using Trizol.
2013-09-05 | E-GEOD-43034 | biostudies-arrayexpress