Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA327121 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Genome-wide siRNA screen of genes regulating the Lipopolysaccharide-induced NF-κB and TNF-α responses in mouse macrophages
| PRJNA327122 | ENA
Project description:Genome-wide siRNA screen of genes regulating the Lipopolysaccharide-induced responses in mammalian macrophages
| PRJNA327114 | ENA
Project description:The mammalian innate immune system senses many bacterial stimuli through the toll-like receptor (TLR) family. Activation of the TLR4 receptor by bacterial lipopolysaccharide (LPS) is the most widely studied TLR pathway due to its central role in host responses to gram-negative bacterial infection and its contribution to endotoxemia and sepsis. Here we describe a genome-wide siRNA screen to identify genes regulating the mouse macrophage TNF-α and NF-κB responses to LPS. We include a secondary validation screen conducted with six independent siRNAs per gene to facilitate removal of off-target screen hits. We also provide microarray data from the same LPS-treated macrophage cells to facilitate downstream data analysis. These data provide a resource for analyzing gene function in the predominant pathway driving inflammatory signaling and cytokine expression in mouse macrophages.
2017-02-23 | GSE83825 | GEO
Project description:The mammalian innate immune system senses many bacterial stimuli through the toll-like receptor (TLR) family. Activation of the TLR4 receptor by bacterial lipopolysaccharide (LPS) is the most widely studied TLR pathway due to its central role in host responses to gram-negative bacterial infection and its contribution to endotoxemia and sepsis. Here we describe a genome-wide siRNA screen to identify genes regulating the human macrophage TNF-α response to LPS. We include a secondary validation screen conducted with six independent siRNAs per gene to facilitate removal of off-target screen hits. We also provide microarray data from the same LPS-treated macrophage cells to facilitate downstream data analysis. These data provide a resource for analyzing gene function in the predominant pathway driving inflammatory cytokine expression in human macrophages.
2017-02-23 | GSE83824 | GEO
Project description:The responses of macrophages to lipopolysaccharide (LPS) might determine the direction of clinical manifestations of sepsis, which is the immune response against severe infection. Meanwhile, the enhancer of zeste homologue 2 (Ezh2), a histone lysine methyltransferase of epigenetic regulation, might interfere with LPS response. With a single LPS stimulation, Ezh2 null(Ezh2flox/flox; LysM-Crecre/−) macrophages demonstrated lower supernatant TNF-α than Ezh2 control (Ezh2fl/fl; LysM-Cre−/−), perhaps due to an upregulation of Socs3, which is a suppressor of cytokine signaling 3, due to the loss of the Ezh2 gene. In LPS tolerance, Ezh2 null macrophages indicated higher supernatant TNF-α and IL-6 than the control, supporting an impact of the loss of the Ezh2 inhibitory gene. In parallel, Ezh2 null mice demonstrated lower serum TNF-α and IL-6 than the control mice after an LPS injection, indicating a less severe LPS-induced hyper-inflammation in Ezh2 null mice. In conclusion, an absence of Ezh2 in macrophages resulted in less severe LPS-induced inflammation, as indicated by low serum cytokines, with less severe LPS tolerance, as demonstrated by higher cytokine production, partly through the upregulated Socs3.
2023-07-20 | PXD041265 | Pride
Project description:<p>During rheumatoid arthritis (RA), TNF activates fibroblast-like synoviocytes (FLS) inducing in a temporal order a constellation of genes, which perpetuate synovial inflammation. Although the molecular mechanisms regulating TNF-induced transcription are well characterized, little is known about the impact of mRNA stability on gene expression and the impact of TNF on decay rates of mRNA transcripts in FLS. To address these issues we performed RNA sequencing and genome-wide analysis of the mRNA stabilome in RA FLS. We found that TNF induces a biphasic gene expression program: initially, the inducible transcriptome consists primarily of unstable transcripts but progressively switches and becomes dominated by very stable transcripts. This temporal switch is due to: a) TNF-induced prolonged stabilization of previously unstable transcripts that enables progressive transcript accumulation over days and b) sustained expression and late induction of very stable transcripts. TNF- induced mRNA stabilization in RA FLS occurs during the late phase of TNF response, is MAPK-dependent, and involves several genes with pathogenic potential such as IL6, CXCL1, CXCL3, CXCL8/IL8, CCL2, and PTGS2. These results provide the first insights into genome-wide regulation of mRNA stability in RA FLS and highlight the potential contribution of dynamic regulation of the mRNA stabilome by TNF to chronic synovitis.</p>
| phs001371 | dbGaP
Project description:HEK293T cells were treated with TNF-alpha for different periods of time to study the effect of siRNA-mediated knockdown of different genes (negative control: Renilla luciferase; positive controls: TNFRSF1A, RelA; gene of interest: CASP4) on TNF-induced gene expression
2012-07-06 | E-MTAB-900 | biostudies-arrayexpress
Project description:Chronic inflammatory diseases are driven by immune cell dysregulation and overproduction of pro-inflammatory molecules, such as tumor necrosis factor alpha (TNFα). Super-enhancers (SEs) and their enhancer RNAs (eRNAs) are critical gene expression regulators and offer therapeutic potential beyond protein-targeting approaches. We hypothesized that targeting eRNAs could reduce chronic inflammation by modulating TNFα expression. We generated TNF-9 knockout (KO) mice by deleting a Tnfα-regulating enhancer region. These mice exhibited significantly reduced Tnfα levels, improved disease outcomes, and diminished immune cell activation in models of rheumatoid arthritis (RA), psoriasis, and lipopolysaccharide (LPS)-induced sepsis. Integrative epigenomic and transcriptomic analysis identified additional LPS-responsive, eRNA-producing enhancers as therapeutic targets. Antisense oligonucleotide (ASO)-mediated knockdown of TNF-9 eRNA in mouse macrophages demonstrated decreased Tnfα expression and alleviated RA symptoms. Furthermore, ASO-mediated inhibition of the eRNA of the human homolog of TNF-9 similarly reduced TNFα levels. These findings support eRNA-targeted interventions as potential treatment for chronic inflammatory diseases.
2025-03-11 | GSE291298 | GEO
Project description:Chronic inflammatory diseases are driven by immune cell dysregulation and overproduction of pro-inflammatory molecules, such as tumor necrosis factor alpha (TNFα). Super-enhancers (SEs) and their enhancer RNAs (eRNAs) are critical gene expression regulators and offer therapeutic potential beyond protein-targeting approaches. We hypothesized that targeting eRNAs could reduce chronic inflammation by modulating TNFα expression. We generated TNF-9 knockout (KO) mice by deleting a Tnfα-regulating enhancer region. These mice exhibited significantly reduced Tnfα levels, improved disease outcomes, and diminished immune cell activation in models of rheumatoid arthritis (RA), psoriasis, and lipopolysaccharide (LPS)-induced sepsis. Integrative epigenomic and transcriptomic analysis identified additional LPS-responsive, eRNA-producing enhancers as therapeutic targets. Antisense oligonucleotide (ASO)-mediated knockdown of TNF-9 eRNA in mouse macrophages demonstrated decreased Tnfα expression and alleviated RA symptoms. Furthermore, ASO-mediated inhibition of the eRNA of the human homolog of TNF-9 similarly reduced TNFα levels. These findings support eRNA-targeted interventions as potential treatment for chronic inflammatory diseases.
2025-03-11 | GSE291297 | GEO