Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA98443 | ENA |
REPOSITORIES: ENA
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Project description:Multiple sclerosis (MS) is an inflammatory disease of the central nervous system and is generally considered to be autoimmune in nature. We previously demonstrated that the transcription factor Sp3 is significantly down-regulated in immune cells from MS patients. The potential role of Sp3 down-regulation in MS pathogenesis is not well understood. The function of endogenous Sp3 was assessed in vitro after siRNA-mediated knockdown of its transcript in Jurkat cells. Sp3 protein levels were reduced an average of 70%. ELISA studies demonstrated decreased endogenous production of IL-10 and TGFβ1 and increased endogenous production of TNFα (p<0.05 in all assays). Subsequent microarray analysis demonstrated significantly altered expression of 36 genes (p<0.001 for each gene) compared with control samples. Analysis showed differential expression (p<0.005) of 8 gene pathways. Many of the genes and pathways that were regulated by Sp3 are involved in immune function, specifically with regard to apoptosis, cell-to-cell adhesion, integrin signaling, T-cell differentiation, and cytokine production. This study identifies mechanisms by which Sp3 may regulate immune function and suggests a basis for its potential contribution to MS disease pathogenesis. Keywords: siRNA knockdown; Jurkat T-cells; Multiple Sclerosis
2008-02-21 | GSE7102 | GEO
Project description:Multiple sclerosis (MS) is an inflammatory disease of the central nervous system and is generally considered to be autoimmune in nature. We previously demonstrated that the transcription factor Sp3 is significantly down-regulated in immune cells from MS patients. The potential role of Sp3 down-regulation in MS pathogenesis is not well understood. The function of endogenous Sp3 was assessed in vitro after siRNA-mediated knockdown of its transcript in Jurkat cells. Sp3 protein levels were reduced an average of 70%. ELISA studies demonstrated decreased endogenous production of IL-10 and TGFβ1 and increased endogenous production of TNFα (p<0.05 in all assays). Subsequent microarray analysis demonstrated significantly altered expression of 36 genes (p<0.001 for each gene) compared with control samples. Analysis showed differential expression (p<0.005) of 8 gene pathways. Many of the genes and pathways that were regulated by Sp3 are involved in immune function, specifically with regard to apoptosis, cell-to-cell adhesion, integrin signaling, T-cell differentiation, and cytokine production. This study identifies mechanisms by which Sp3 may regulate immune function and suggests a basis for its potential contribution to MS disease pathogenesis. Experiment Overall Design: Two Sp3 siRNA knockdown groups (siRNA Sp3 #2: n=3, and #6: n=3) were clustered together into the Treated condition, and the two control groups (siRNA for GAPDH: n=3, and Non-transfected cells: n=3)were assembled to constitute the Control condition. Thus a total of 12 arrays (6 Controls and 6 treated) were used in this experiment.
2008-04-07 | E-GEOD-7102 | biostudies-arrayexpress
Project description:SP1 and SP3 have been reported to play an critical role in the pregression of tumors. In order to elucidate the molecular mechanism of SP1 and SP3 in colorectal cancer, RNA-seq analysis was performed on SP1 and SP3 knockdown and control HCT116 cells.
2024-07-01 | GSE179314 | GEO
Project description:The histone deacetylase HDAC2, which negatively regulates neuronal plasticity and synaptic gene expression, is upregulated both in Alzheimer’s disease (AD) patients and mouse models (Graff et al., 2012). Therapeutics targeting HDAC2 are speculated to be a promising avenue for ameliorating AD related cognitive impairment. However, attempts to generate HDAC2-specific inhibitors have not been successful. Here, we take a novel approach utilizing integrative genomics to identify proteins that mediate HDAC2 recruitment to synaptic plasticity genes. Functional screening revealed that knockdown of the transcription factor Sp3 phenocopied HDAC2 knockdown, and that Sp3 facilitated the recruitment of HDAC2 to synaptic genes. Importantly, like HDAC2, Sp3 expression was elevated in AD patients and mouse models, where Sp3 knockdown ameliorated synaptic dysfunction. Furthermore, exogenous expression of an HDAC2 fragment containing the Sp3 binding domain fully restored synaptic plasticity and memory in a mouse model with severe neurodegeneration. Our findings indicate that targeting the HDAC2-Sp3 complex could enhance synaptic and cognitive function, without affecting HDAC2 function in other processes.
2017-08-08 | GSE87441 | GEO
Project description:Purpose: Next-Generation Sequencing (NGS) RNA was subjected to analysis genome-wide expression. The goals of this study are to identify differentially expressed genes in CXCR4 knockout macrophages compared to CXCR4-expressed macrophages. Methods: Total RNA of macrophage transfected with CXCR4 siRNA (MΦsiCXCR4) or siRNA negative control (MΦsiNC), then, stimulated with 100ng/ml lipopolysaccharide (LPS) for 12 hours. Preparation of library and sequencing of transcriptome was performed by Illumina NovaSeq 6000. Results: A large number of differentially expressed genes were screened by high-throughput sequencing at the genome-wide level using RNA-Seq technology. Loss of CXCR4 in bone-marrow-derived macrophages results in attenuated pro-inflammatory cytokine and decorin production under LPS stimulation compared to control macrophages. Conclusions: Our study reveals that CXCR4 orchestrated the pro-inflammatory cytokine and decorin production in macrophages.
2023-08-06 | GSE182050 | GEO
Project description:Interleukin-27 (IL27) is a type-I-cytokine of the IL6/IL12 family predominantly secreted by activated macrophages and dendritic cells. Best understood are the effects of IL27 on immune cells where it has been described to have pro- or anti-inflammatory properties, either promoting TH1 responses or suppressing TH1 and TH2 responses. The action on other cell types is less well studied. In the liver, IL27 expression was observed to be upregulated in patients with hepatitis B, and sera of hepatocellular carcinoma (HCC) patients contain significantly elevated levels of IL27 compared to healthy controls or patients with hepatitis and/or liver cirrhosis. We previously reported interferon-gamma-like antiviral activity of IL27 in hepatic cells. Here we further studied the effects of IL27 on HCC cells in comparison to other cytokines. We were especially interested in the relevance of the IL27-induced STAT3 activation. Thus we compared its response with those induced by IFNg (STAT1-dominated response) or IL6-type cytokines (IL6, Hyper-IL6 or OSM) (STAT3-dominated response). We find that in hepatocytes, IL27 induces an IFNg-like, STAT1-dependent transcriptional response, but we do not find an effective STAT3-dependent response. The availability of STAT1 seems critical in the shaping of the IL27 response, as the siRNA knock-down of STAT1 revealed its ability to induce the acute-phase protein gamma-fibrinogen, a typical IL6 family characteristic. Moreover, we describe a crosstalk between the signaling of IL6-type cytokines and IL27: responses to the gp130-engaging cytokine IL27 (but not those to IFNs) can be inhibited by IL6-type cytokine pre-stimulation, likely by a SOCS3-mediated mechanism. This experiment represents microarray analysis of three hepatocellular carcinoma cell lines treated with IL-27, IFNg, hyper-IL6 or OSM in combination with shRNA knockdown of STAT3.
2017-07-05 | E-MTAB-4570 | biostudies-arrayexpress
Project description:Members of the Sp family of transcription factors regulate gene expression via binding GC boxes within promoter regions. Unlike Sp1, which stimulates transcription, the closely related Sp3 can either repress or activate gene expression and is required for perinatal survival in mice. Here we use RNAseq and cellular phenotyping to show how Sp3 regulates murine fetal cell differentiation and proliferation. Homozygous Sp3-/- mice were smaller than WT and Sp+/- littermates, died soon after birth, and had abnormal lung morphogenesis. RNAseq of Sp3-/- fetal lung mesenchymal cells identified alterations in extracellular matrix production, developmental signaling pathways, and myofibroblast/lipofibroblast differentiation. The lungs of Sp3-/- mice contained multiple structural defects, with abnormal endothelial cell morphology, lack of elastic fiber formation, and accumulation of lipid droplets within mesenchymal lipofibroblasts. Sp3-/- cells and mice also displayed cell cycle arrest, with accumulation in G0/G1 and reduced expression of numerous cell cycle regulators including Ccne1. These data detail the global impact of Sp3 on in vivo mouse gene expression and development. Development • Accepted manuscript lung mesenchymal cells identified alterations in extracellular matrix production, developmental signaling pathways, and myofibroblast/lipofibroblast differentiation. The lungs of Sp3-/- mice contained multiple structural defects, with abnormal endothelial cell morphology, lack of elastic fiber formation, and accumulation of lipid droplets within mesenchymal lipofibroblasts. Sp3-/- cells and mice also displayed cell cycle arrest, with accumulation in G0/G1 and reduced expression of numerous cell cycle regulators including Ccne1. These data detail the global impact of Sp3 on in vivo mouse gene expression and development.
2023-02-28 | GSE225703 | GEO
Project description:IL-33 is a nuclear cytokine from the IL-1 family that plays important roles in health and disease. Under healthy conditions, IL-33 is constitutively expressed to high levels in the nucleus of producing cells in various human and mouse tissues. The extracellular function of IL-33 cytokine has been well documented, but it remains unclear whether intracellular nuclear IL-33 has additional functions in the nucleus. Here, we used a global proteomic approach based on quantification of 5000 individual proteins by high-resolution mass spectrometry to compare the extracellular and intracellular roles of IL-33 in primary human endothelial cells, a major source of IL-33 protein in human tissues. Large-scale analysis of protein expression was performed either after stimulation of the cells with the IL-33 mature form IL-3395-270 (during 6h or 24h) or after siRNA knockdown of intracellular IL-33 (two experiments, each with a different pool of distinct siRNAs, noted siRNA1 and siRNA2). In each case, proteins were fractionated by 1D SDS-PAGE in 12 gel bands, and label-free quantitative analysis was performed. The present dataset contains the files for the two experiments of knockdown of endogenous nuclear IL-33 expression: - RNA silencing strategy 1. Knockdown of endogenous nuclear IL-33 expression was performed with a pool of four distinct siRNAs (Dharmacon ON-TARGETplus SMARTpool IL-33 siRNAs) that have been specifically modified for efficient silencing of the target gene with reduced off-target effects. Cells transfected with these siRNA duplexes (si1) were compared with those transfected with the provided controls (CTsi1). Three independent biological replicates (noted _A, _B, _C) were prepared and analyzed for each condition, leading to 6 different samples. Each of them was fractionated into 12 gel bands analyzed by nanoLC-MS/MS, leading to 72 raw files. - RNA silencing strategy 2. The second knockdown strategy was based on the use of an independent pool of three siRNAs targeting IL-33, predesigned by another provider using new and critical siRNA design rules (Sigma MISSION Predesigned Il-33 siRNAs based on Rosetta siRNA design algorithm). Cells transfected with these siRNA duplexes (si2) were compared with those transfected with the provided controls (CTsi2). Three independent biological replicates (noted _A, _B, _C) were prepared and analyzed for each condition, leading to 6 different samples. Each of them was fractionated into 12 gel bands analyzed by nanoLC-MS/MS, leading to 72 raw files.
2016-10-12 | PXD004141 | Pride
Project description:NFAM1 promotes pro-inflammatory cytokine production in mouse and human monocytes.
| PRJNA778714 | ENA
Project description:Bromodomain-containing proteins bind acetylated lysine residues on histone tails and are involved in the recruitment of additional factors that mediate histone modifications and enable transcription. A compound, I-BET-762, that inhibits binding of an acetylated histone peptide to BRD4 and other proteins of the BET (bromodomain and extra-terminal domain) family, was previously shown to suppress the production of pro-inflammatory proteins by macrophages and block acute inflammation in mice. Here we investigate the effect of I-BET-762 on T cell function. We show that treatment of naïve CD4+ T cells with I-BET-762 during early differentiation modulates subsequent cytokine production, and inhibits the ability of Th1-skewed cells to induce autoimmune pathogenesis in a model of experimental autoimmune encephalomyelitis (EAE) in vivo. The suppressive effects of I-BET-762 on T-cell mediated inflammation were not due to inhibition of expression of the pro-inflammatory cytokines, IFN-. or IL-17, but correlated with the ability to suppress GM-CSF production from CNS-infiltrating T cells, resulting in decreased recruitment of macrophages and granulocytes. The effects of I-BET-762 were distinct from those of the fumarate ester, dimethyl fumarate (DMF), a candidate drug for treatment of multiple sclerosis (MS). Our data suggest that I-BET and DMF could have complementary roles in the treatment of MS, and provide a strong rationale for inhibitors of BET-family proteins in the treatment of autoimmune diseases, based on their dual ability to suppress granulocyte and macrophage recruitment by T cells as well as production of pro-inflammatory proteins by macrophages. RNA from resting or activated CD4+ T cells grown in the presence of a control substance (DMSO or Control-768) or two different concentrations of I-BET-762, was hybridized to the chip. There are 3 biological replicates for a total of 2 (cell states) x 4 (conditions) x 3 (replicates) = 24 samples.
2012-08-03 | E-GEOD-39886 | biostudies-arrayexpress