Mus musculus
Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: E-GEOD-23421
PROVIDER: PRJNA131037 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Inflammatory bowel disease (IBD) is a condition characterized by severe intestinal inflammation and immune cell activation. The severity of the disease can be mitigated by compounds which activate peroxisome proliferator-activated receptor gamma (PPAR gamma), a receptor present widely in tissues involved in IBD pathogenesis. Our objective was to assess the affect of macrophage-specific deficiency of PPAR gamma on peripheral and colonic immune populations and colonic gene expression in experimental IBD. Macrophage-specific PPAR gamma-deficient mice (PPAR gamma flfl Lysozyme M Cre+) and control (PPAR gamma flfl Lysozyme M Cre-) littermates were treated with 2.5% dextran sodium sulfate (DSS) for 7 days. Disease activity was recorded daily and immune cell populations in the blood, spleen, mesenteric lymph nodes (MLN), and lamina propria were examined by flow cytometry. Colonic gene expression was assessed by real time PCR and microarray analyses. Our findings show that macrophage PPAR r-deficiency significantly exacerbates DSS inflammation. CD4+CD25+FoxP3+ regulatory T cells (T-regs) were significantly reduced in Cre+ mice, and MLN macrophages and CD40 expression were enhanced. There were significant differences in the number colonic macrophages between Cre+ and Cre- mice, but those from Cre+ mice expressed more CD40, Ly6C, and TLR-4. PPAR r-deficiency also increased the percent of CD8+ T cells in the lamina propria and enhanced colonic interferon gamma expression. Our findings indicate that macrophage PPAR gamma deficiency augments the severity of DSS colitis by reducing peripheral T-regs and increasing colonic macrophage activation and T cell inflammation. RNA from 3 PPAR gamma-deficient mice (PPAR gamma flfl; Lysozyme M Cre+) and 3 control (PPAR gamma flfl; Lysozyme M Cre-) littermates was processed and labeled according to the standard target labeling protocols. The samples were hybridized, stained, and scanned per standard Affymetrix protocols at the Virginia Bioinformatics Institute (VBI) core laboratory on Mouse 430 2.0 expression arrays (Affymetrix Inc., Santa Clara, CA).
2011-11-12 | E-GEOD-23421 | biostudies-arrayexpress
Project description:Inflammatory bowel disease (IBD) is a condition characterized by severe intestinal inflammation and immune cell activation. The severity of the disease can be mitigated by compounds which activate peroxisome proliferator-activated receptor gamma (PPAR gamma), a receptor present widely in tissues involved in IBD pathogenesis. Our objective was to assess the affect of macrophage-specific deficiency of PPAR gamma on peripheral and colonic immune populations and colonic gene expression in experimental IBD. Macrophage-specific PPAR gamma-deficient mice (PPAR gamma flfl Lysozyme M Cre+) and control (PPAR gamma flfl Lysozyme M Cre-) littermates were treated with 2.5% dextran sodium sulfate (DSS) for 7 days. Disease activity was recorded daily and immune cell populations in the blood, spleen, mesenteric lymph nodes (MLN), and lamina propria were examined by flow cytometry. Colonic gene expression was assessed by real time PCR and microarray analyses. Our findings show that macrophage PPAR r-deficiency significantly exacerbates DSS inflammation. CD4+CD25+FoxP3+ regulatory T cells (T-regs) were significantly reduced in Cre+ mice, and MLN macrophages and CD40 expression were enhanced. There were significant differences in the number colonic macrophages between Cre+ and Cre- mice, but those from Cre+ mice expressed more CD40, Ly6C, and TLR-4. PPAR r-deficiency also increased the percent of CD8+ T cells in the lamina propria and enhanced colonic interferon gamma expression. Our findings indicate that macrophage PPAR gamma deficiency augments the severity of DSS colitis by reducing peripheral T-regs and increasing colonic macrophage activation and T cell inflammation.
2011-11-12 | GSE23421 | GEO
Project description:Cadaverine is a polyamine produced by the gut microbiota with links to health and disease, notably inflammatory bowel disease (IBD). Here, we show that cadaverine shapes monocyte-macrophage immunometabolism in a context- and concentration-dependent fashion to impact macrophage functionality. At baseline, cadaverine is taken up via L-lysine transporters and activates the thioredoxin system, while during inflammation, cadaverine signals through aconitate decarboxylase 1 (Acod1)-itaconate. Both pathways induce activation of transcription factor, nuclear factor erythroid 2-related factor 2 (Nrf2), which supports mitochondrial respiration and promotes immunoregulatory macrophage polarization. Conversely, under higher concentrations, cadaverine acts via histamine 4 receptor, leading to glycolysis-driven inflammation and pro-inflammatory functions in macrophages. Likewise, cadaverine exhibits paradoxical effects in experimental colitis, either protective or detrimental, evoking opposite fates on macrophages depending on levels dictated by Enterobacteriaceae. In IBD patients, elevated cadaverine correlated with higher flare risk. Our findings implicate cadaverine as a microbiota-derived metabolite manipulating macrophage energy metabolism with consequences in intestinal inflammation and implications for IBD pathogenesis.
2025-10-06 | PXD057652 | Pride
Project description:Background: Cellular senescence has emerged as a key contributor to the pathogenesis of chronic lung diseases. Peroxisome proliferator-activated receptor gamma (PPAR-γ), a nuclear transcription factor, regulates senescence across multiple cell types. However, the role of PPAR-γ in allergic airway inflammation, particularly through regulation of macrophage senescence, remains poorly defined. Methods: Cellular senescence was evaluated in an allergic asthma mouse model using single-cell RNA sequencing (scRNA-seq). Senescent cells were selectively eliminated with dasatinib and quercetin (D&Q) to assess their contribution to disease pathogenesis. Macrophage-lineage-specific PPAR-γ conditional knockout model (PpargΔCD11c) were generated to define the role of macrophage PPAR-γ in senescence and allergic airway inflammation. PPAR-γ activity was further examined in isolated alveolar macrophages and in vivo using rosiglitazone, including macrophage-targeted delivery via phosphatidylserine-modified liposomes (PSL-ROSI). Findings: scRNA-seq analysis revealed enhanced senescence signatures in mononuclear phagocytes (MNPs), characterized by increased SenMayo scores and elevated Cdkn2a (p16) expression. Clearance of senescent cells significantly reduced airway inflammation and Th2 cytokine levels (IL-4, IL-5). Correlation analysis identified PPAR-γ as a key transcriptional regulator inversely associated with cellular senescence. Macrophage-lineage–specific deletion of PPAR-γ (PpargΔCD11c) exacerbated airway inflammation and increased cellular senescence. In vitro, rosiglitazone reduced allergen-induced senescence and suppressed proinflammatory mediators (IL-6, ICAM-1, CCL4, CCL5, TIMP-1, TNF-α) in alveolar macrophages. In vivo, rosiglitazone and inhaled PSL-ROSI attenuated cockroach allergen-induced airway inflammation, with PSL-ROSI effectively bypassing the airway mucus barrier to deliver rosiglitazone to lung macrophages. Integrated chromatin binding and transcriptomic analyses demonstrated that PPAR-γ promotes macrophage lipid metabolic programs (e.g., CD36, Fabp4). Interpretation: These findings identify macrophage senescence as a pathogenic driver of allergic airway inflammation and establish PPAR-γ as a critical regulator of macrophage senescence and homeostasis, highlighting its potential as a therapeutic target for asthma.
2026-03-16 | GSE322708 | GEO
Project description:Ligand-mediated activation of the nuclear hormone receptor PPAR gamma lowers blood pressure and improves glucose tolerance in humans. Two naturally occurring mutations (P467L, V290M) in the ligand binding domain of PPAR gamma have been described in humans that lead to severe insulin resistance and hypertension. Experimental evidence suggests that these mutant versions of PPAR gamma act in a dominant negative fashion. To better understand the molecular mechanisms underlying PPAR gamma action in the vasculature, we determined the global gene expression profile in primary aortic endothelial cells in response to endothelial cell specific expression of a dominant negative isoform of PPAR gamma (V290M).
2008-07-23 | GSE11870 | GEO
Project description:BACKGROUND: Peroxisome proliferator-activated receptor g (PPAR g) is a nuclear receptor whose activation has been shown to modulate macrophage and epithelial cell-mediated inflammation. The objective of this study was to use a systems approach for investigating the mechanism by which the deletion of PPAR g in T cells modulates the severity of dextran-sodium sulfate (DSS)-induced colitis, immune cell distribution and global gene expression. METHODS: Wild-type (WT) or PPAR g flfl; CD4 Cre+ (CD4cre) mice in a C57BL/6 background were challenged with 2.5% DSS in their drinking water for 0, 2, or 7 days. Mice were scored on disease severity both clinically and histopathologically. Flow cytometry was used to assess lymphocyte and macrophage populations in the blood, spleen, and mesenteric lymph nodes (MLN). Global gene expression in colonic mucosa was profiled using Affymetrix microarrays. RESULTS: Both disease severity and inflammation-related body weight loss were accelerated by the deficiency of PPAR g in T cells. Examination of colon histopathology revealed significantly greater epithelial erosion, leukocyte infiltration, and mucosal thickening in the CD4cre mice on day 7. CD4cre mice had more CD8+ T cells than wt mice and fewer CD4+FoxP3+ regulatory T cells (Treg) and IL10+CD4+ T cells in blood and MLN, respectively. Transcriptomic profiling revealed around 3000 genes being transcriptionally altered as a result of DSS challenge in CD4cre mice. These included up-regulated adhesion molecules on day 7 and proinflammatory cytokines interleukin-6 (IL-6) and IL-1b, and suppressor of cytokine signaling 3 (SOCS-3) mRNA expression. CONCLUSIONS: These findings suggest that T cell PPAR g down-regulates inflammation during DSS colitis by inhibiting colonic expression of inflammatory mediators and increasing MLN Treg. Colonic mucosa from wt and CD4cre mice were sampled at 0 (no DSS), 2, and 7 days of DSS-induced experimental colitis
2010-07-08 | E-GEOD-20523 | biostudies-arrayexpress
Project description:Macrophages are known to be polarized into inflammatory (M1) and immunoregulatory (M2) cells when they are stimulated by agonists such as IFN-gamma and IL-4, respectively. If circulating monocytes may be polarized in response to T cell signals is often misguidedly deduced from macrophage results. Here the transcriptional responses of human CD14+ monocytes to IFN-gamma and IL-4 were analyzed using whole genome microarrays. A principal component analysis and hierarchical clustering showed that monocyte and macrophage responses were distinct. Monocytes stimulated with IFN-gamma and IL-4 for 6 hours exhibited some features of macrophage polarization. Indeed, when 80 genes considered as M1 and M2 genes were analyzed, we found that M1 genes were modulated in response to IFN-gamma and that M2 genes were modulated in response to IL-4. The M1 polarization of monocytes was transient because only M2 genes were modulated when monocytes were stimulated with IFN-gamma and IL-4 for 18 hours. However, the activation of monocytes by IFN-gamma and IL-4 could not be reduced to M1/M2 polarization status. Indeed, monocytes exhibited early specific signatures composed of 46 and 39 up-regulated genes in response to IFN-gamma and IL-4, respectively, and a late signature common to both molecules that consisted of 57 up-regulated genes. Taken together, these results demonstrated the extreme plasticity of human monocytes and suggested the existence of a core transcriptional termination program. Using early and late signatures might be pertinent to investigate monocyte activation in inflammatory or infectious diseases. Monocytes were stimulated with IFN-gamma (20ng/mL) or IL-4 (20ng/mL) for 6 and 18 hours or culture for 6 and 18 hours without agonist (Unstimulated samples). Monocytes-derived-macrophages (MDM) stimulated with IFN-gamma and IL-4 for 18 hours were used as controls. Each microarray is derived from a single biological sample.
2013-03-15 | E-GEOD-36537 | biostudies-arrayexpress
Project description:Pro-inflammatory activation of macrophages promotes various inflammatory disorders. The molecular mechanisms underlying macrophage activation, particularly in the context of nuclear translocation of pro-inflammatory response mediators, remain obscure. We have used a systems approach to explore key regulators of macrophage activation using quantitative proteomics to monitor protein translocation to the nuclei of human primary macrophages elicited with interferon γ (IFN-γ). Unbiased bioinformatics identified several candidates, including RSK1, a ribosomal protein kinase. Network analysis linked RSK1 with human gene modules for various inflammatory disorders. In vitro mechanistic experiments showed that IFN-γ stimulation promotes RSK1 phosphorylation at Ser380 via JAK signaling, resulting in STAT1 phosphorylation at Ser727, in the nuclei of macrophages. In concert with these results, RSK1 silencing or deficiency hinders IFN-γ-induced secretion of pro-inflammatory chemokines in human primary macrophages. Furthermore, RSK1 deficiency in human leukocytes altered IFN-γ-induced responses in humanized mice. Our findings provide evidence that RSK1 is a key nuclear shuttling enzyme that mediates pro-inflammatory activation of macrophages.
2026-07-08 | PXD069750 | Pride
Project description:Rationale: Chronic obstructive pulmonary disease (COPD) features persistent airway inflammation, oxidative/nitrative stress, and macrophage activation. γ-tocopherol has antioxidant and anti-inflammatory activity, but its disease relevance and molecular targets are unclear. Objectives: To test whether γ-tocopherol attenuates disease-associated inflammation and define the macrophage mechanism. Methods: Multi-omics integrated analysis combined with γ-tocopherol-treated COPD-like mouse models was performed to evaluate the anti-inflammatory effects of γ-tocopherol and identify its target cell populations. Furthermore, target prediction, cellular thermal shift assay, co-immunoprecipitation, and other experimental approaches were used to identify the molecular target of γ-tocopherol and elucidate the downstream mechanisms underlying its anti-inflammatory and antioxidant effects. Measurements and Main Results: COPD was associated with altered γ-tocopherol metabolism and vitamin E-related transcriptional programs. γ-tocopherol reduced inflammatory cell accumulation, nitric oxide metabolites, macrophage activation, and lung inflammation in COPD-like mouse models. Alveolar macrophages were identified as the primary target cell population of γ-tocopherol in lung tissue. γ-tocopherol treatment suppressed nitric oxide synthesis and inflammatory cytokine release in macrophages, and this effect depended on the engagement of γ-tocopherol with PSEN1. Further mechanistic analysis identified SYT7 as a downstream effector of PSEN1, linking γ-tocopherol treatment to reduced PI3K/AKT signaling activity and attenuated inflammatory readouts. Conclusions: γ-tocopherol attenuates macrophage-centered inflammation in COPD-like models through a PSEN1–SYT7–PI3K/AKT signaling axis.
2026-06-26 | GSE336580 | GEO
Project description:Dysregulated tissue-resident macrophages (TRMs) contribute to pathogenesis of inflammatory bowel disease (IBD) and multiple sclerosis (MS), yet the molecular pathways that regulates TRMs remain unclear. Smurf2 deficiency significantly exacerbates the TRM proliferation in dextran sulfate sodium (DSS)-induced colitis and experimental autoimmune encephalomyelitis (EAE), leading to augmented autoimmune inflammation.
2026-02-11 | GSE307224 | GEO