Immunoregulatory actions of epithelial cell PPAR g at the colonic mucosa
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE20621 | GEO | 2010/06/21
SECONDARY ACCESSION(S): PRJNA124807
REPOSITORIES: GEO
Similar Datasets
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 epithelial cells modulates the severity of dextran-sodium sulfate (DSS)-induced colitis, immune cell distribution and global gene expression. RESULTS: The deficiency of PPAR g in epithelial cells does not significantly affect disease activity or body weight but worsens colon histopathlogy. WT mice have greater CD4+IL10+ T cells and fewer MHC II+ macrophages in mesenteric lymph nodes. Global gene expression analysis reveals greater changes after 7 days of DSS challenge (compared to 2 days). Colonic mucosa from VC- (WT) and VC+ (PPARg knock-out in epithelial cells) mice were sampled at 0 (no DSS), 2, and 7 days of DSS-induced experimental colitis
2010-07-08 | E-GEOD-20621 | biostudies-arrayexpress
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: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.
2010-06-21 | GSE20523 | GEO
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:The aim of this study is to compare the transcriptomic profile of colonic intestinal epithelial cells (IECs) at steady-state, and in several models of colitis: in naive wild-type C57BL/6 mice, in wild-type C57BL/6 mice treated for 7 days with 3% dextran sodium sulfate (DSS) in drinking water, in Il10-/- C57BL/6 mice and Il10-/- C57BL/6 mice with IEC-specific Rabgef1 deletion. Colonic IECs were isolated and FACS-sorted, then subjected tu bulk RNA-seq.
2019-09-30 | E-MTAB-7315 | biostudies-arrayexpress
Project description:We performed gene expresion analysis of T cell treated with agonist of three isoform of PPAR. This analysis allowed us to explain why the activation of PPAR g is the best in boosting PD-1 blockade efficacy compared with other isoform activation. We demonstrated that activation of the PPAR-γ isoform specifically enhanced PD-1 blockade greater than activation of the other two PPAR isoforms (a and b) in mouse tumor model. Using the microarray assay we found genes that were most differentially regulated by PPAR agonist treatment were with a well-documented role in T cell biology, such as Ddx3y, Ifng, Il17c, Ccr3, Acrv1, Btk and metabolic process such as Pygl, P2rx1, Tph2, Kynu, and Ugt2b37. Therefore, microarray data has been useful to establish that activation of PPAR-g in T cell uniquely modulate genes, which include metabolic as well genes related to immune function.
2020-12-06 | GSE162721 | GEO
Project description: Not available
| S-EPMC2857885 | biostudies-literature
Project description:We took a systematic approach to determine the transcriptional programs that are specifically regulated by C/EBP? in mature white adipocytes of mice on chow diet or high fat diet. The hypothesis tested in the present study was that C/EBP?, as a lipogenic transcription factor, has unique direct targets compared to PPAR?. Our inducible adipocyte specific knockout system allows us to test the direct targets of C/EBP? and PPAR? in adipocytes by short-term C/EBP? or PPAR? elimination in mature adipocytes in vivo. Results indicate that although it has been shown that C/EBP? and PPAR? cross-regulate each other, they have distinct direct responsive targets. Moreover, there are very few C/EBP? specific targets in mice on a chow diet, most of the C/EBP? targets in mature adipocytes are genes modulated by HFD feeding. Total RNA obtained from subcutaneous adipose tissue of Adn-C/EBP?-/- mice on doxycycline chow diet for 3 days, doxycycline high fat diet for 3 days or 1 month and Adn-PPAR?-/- mice on doxycycline chow diet for 3 days, compared to control littermates.
2014-11-04 | E-GEOD-62937 | biostudies-arrayexpress
Project description:Aims: To compare the molecular and biologic signatures of a balanced dual peroxisome proliferator-activated receptor-α/γ (PPAR-α/γ) agonist, aleglitazar, with tesaglitazar (a dual PPAR-α/γ agonist) or combination of pioglitazone (PPAR-γ agonist)/fenofibric acid (PPAR-α agonist) in human hepatocytes. Methods and Results: Gene expression microarray profiles were obtained from primary human hepatocytes treated with EC50-aligned low, medium, and high concentrations of the three treatments. A systems-biology approach, Causal Network Modeling, was used to model the data to infer upstream molecular mechanisms that may explain the observed changes in gene expression. Aleglitazar, tesaglitazar and pioglitazone/fenofibric acid, each induced unique transcriptional signatures, despite comparable core PPAR signaling. Although all treatments inferred qualitatively similar PPAR-α signaling, aleglitazar was inferred to have greater effects on high- and low-density lipoprotein cholesterol levels than tesaglitazar and pioglitazone/fenofibric acid, due to greater number of gene expression changes in pathways related to HDL and LDL metabolism. Distinct transcriptional and biologic signatures were also inferred for stress responses, which appeared to be less affected by aleglitazar than the comparators. In particular, pioglitazone/fenofibric acid was inferred to increase NFE2L2 activity, a key component of the stress response pathway, while aleglitazar had no significant effect. All treatments were inferred to decrease proliferative signaling. Conclusions: Aleglitazar induces transcriptional signatures related to lipid parameters and stress responses that are unique from other dual PPAR-α/γ treatments. This may underlie observed favorable changes in lipid profiles in animal and clinical studies with aleglitazar and suggests a differentiated gene profile compared with other dual PPAR-α/γ agonist treatments.
2011-10-22 | GSE33152 | GEO