Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA327122 | ENA |
REPOSITORIES: ENA
Similar Datasets
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:Genome-wide siRNA screen of genes regulating the Lipopolysaccharide-induced TNF-α response in human macrophages
| PRJNA327121 | 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 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:We applied ChronoSeq to profile inflammatory responses in K562 cells stimulated with TNF-α, to capture the rapid NF-κB signaling cascade. 10 minute interval between samples including a 1 minute sampling duration. In addition Puromycin was added at a does of 5μg/ml for blocking translation. The purpose of this experiment was to measure TNF-α stimulation transcriptional program without translational feedback.
2025-11-01 | E-MTAB-15947 | biostudies-arrayexpress
Project description:Medicinal plants have shown great promise as a source of novel drug compounds for the treatment of inflammatory disorders. In our search for new entities with anti-inflammatory potential, the extracts of the whole plant of Saussurea heteromalla (family-Asteraceae), collected from Himalayas, were evaluated in the high throughput screen for TNF-α and IL-6 inhibitors. The plant has been found as a new source of chlorojanerin, a guaianolide type of sesquiterpene lactone. This is the first report on the potent anti-inflammatory activity of the compound. Chlorojanerin was shown to be significantly effective in inhibiting TNF-α and IL-6 production in LPS induced THP-1 cells (TNF-α, IC50 = 3µM and IL-6, IC50 = 0.8µM). The compound also blocked TNF-α and IL-6 production from LPS induced human monocytes and synovial cells from RA patients. Chlorojanerin also inhibited the binding of NF-κB in a GFP reporter assay system. Transcriptional profiling of the LPS stimulated THP-1 cells revealed that chlorojanerin exerted its anti-inflammatory effect by inhibiting the expression of genes involved in activating the transcription factor – NF-κB. Real time analysis of these genes validated the effect of chlorojanerin on the classical downstream targets of NF-κB. Thus, this study clearly delineated 8 targets specific for the effect of chlorojanerin on NF-κB induced signaling at the mRNA level. This work is a step towards the isolation and characterization of lead anti-inflammatory agents from the extract of Saussurea heteromalla, which can be developed into better therapeutic molecules targeted towards some specific inflammatory diseases. Single dye labelling with Cy3 for all treatment RNA samples. Treatments included unstimulated, LPS stimulated, Chlorjanerin treatment and dexamethasone treatment.
2011-12-14 | E-GEOD-34180 | biostudies-arrayexpress
Project description:Genome-wide siRNA screen of genes regulating the Lipopolysaccharide-induced responses in mammalian macrophages
| PRJNA327114 | ENA
Project description:Objective: To evaluate the protective effects of marine cyclopeptide galaxamide against cisplatin-induced uterine toxicity in cervical cancer models, focusing on macrophage polarization and NF-κB signaling modulation Methods: In vivo tumor-bearing mouse models and in vitro cervical cancer cell lines were treated with cisplatin (CIS, 5 mg/kg) ± galaxamide (20 mg/kg). Uterine histopathology (hematoxylin-eosin staining), apoptosis (TUNEL assay), macrophage subsets (flow cytometry for M1/M2 markers), NF-κB activation (western blot for p65 phosphorylation), and serum cytokines (ELISA for TNF-α/IL-6) were analyzed. Embryo implantation rates were assessed to quantify endometrial receptivity Results: Cisplatin caused significant endometrial atrophy (↓45% thickness vs. control, P<0.01), NF-κB hyperactivation (2.8-fold p65 increase), and M1-macrophage dominance (M1/M2 ratio ↑40%). These changes correlated with elevated pro-inflammatory cytokines (TNF-α↑300%, IL-6↑180%) and reduced embryo implantation (↓67%, P<0.001). Galaxamide co-treatment: Suppressed NF-κB activation (p65↓65%, P<0.01) and apoptosis (TUNEL+ cells↓50%) Restored M2-macrophages (↑25%, P<0.05) and cytokine balance (TNF-α↓55%, IL-6↓48%) Preserved endometrial integrity and increased implantation rates (1.9-fold vs. CIS alone, P<0.01) Conclusion: Galaxamide mitigates cisplatin-induced uterine damage by reprogramming macrophages toward M2 phenotype and inhibiting NF-κB-mediated inflammation, offering a promising adjuvant strategy to preserve fertility in young cervical cancer patients Keywords: cisplatin toxicity, uterine protection, galaxamide, macrophage polarization, NF-κB pathway
2026-09-01 | GSE302127 | GEO
Project description:Cordyceps participates in various pharmacological activities including anti-tumor, and is involved in the regulation of NF-κB signaling pathway. However, the detailed role of cordycepin in suppression of NF-κB signaling pathway is less clear. In this study, we first analyzed the effect of cordyceps on NF-κB activity in TK-10 cells, and found that cordyceps resulted in a dose-dependent reduction in TNF-α-induced NF-κB activation. Here, we show that cordyceps mediated NF-kB inhibition induces apoptosis in TK-10 cells involved the serial activation of caspases. Moreover, we demonstrate that in addition to activating caspases, the cordyceps negatively modulates TNF-α-mediated NF-κB signaling to promote JNK activation, which results in apoptosis, and that NF-kB regulates antiapoptotic factor GADD45b and the JNK kinase MKK7. When the TNFα cytokine binds to the TNF receptor, IκB dissociates from NF-κB. As a result, the active NF-κB translocates to the nucleus. Cordyceps clearly prevented NF-κB from mobilizing to the nucleus, resulting in downregulation of GADD45b, whereas upregulation of MKK7 and phosphorylation of JNK (p-JNK). This increased Bax activation, leading to marked cordyceps-induced apoptosis. Bax subfamily proteins induced apoptosis through caspase-3. Furthermore, siRNA mediated inhibition of MKK7 downregulated p-JNK and The JNK inhibitor SP600125 strongly inhibited Bax. Thus, these results indicate that cordyceps inhibits NF-κB/GADD45b signaling activation to upregulate MKK7-JNK signaling pathway to induce apoptosis in TK-10 cells and support the potential of cordyceps as a therapeutic agent for renal cancer.
2016-05-24 | GSE81728 | GEO
Project description:The bacterial product lipopolysaccharide (LPS) stimulates nuclear factor kB (NF-kB) signaling, which results in the production of proinflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha), as part of the immune response. NF-kB target genes also include those encoding proteins that inhibit NF-kB signaling through negative feedback loops. By simultaneously studying the dynamics of the nuclear translocation of the NF-kB subunit RelA and the activity of a Tnf-driven reporter in a mouse macrophage cell line, Sung et al. found that the gene encoding RelA was also a target of NF-kB. Synthesis of RelA occurred only at higher concentrations of LPS and constituted a positive feedback loop that dominated over existing negative feedback mechanisms. Genes expressed in response to a high concentration of LPS were enriched for those involved in innate immune responses. Together, these data suggest that the RelA-dependent positive feedback loop enables macrophages to mount an effective immune only above a critical concentration of LPS. Bone-marrow-derived macrophage (BMDM) cells were stimulated with zero, low, and high concentration of LPS separately for 4hrs. Two replicates for each condition.
2014-01-14 | E-GEOD-53810 | biostudies-arrayexpress
Project description:The model was constructed to describe TLR4 induced NF-κB activation in native bone marrow-derived macrophages. It included processes of ligand (lipopolysaccharide) recognition, formation of dimer receptor complex and further signal transduction through TRAF6/TAK1 complex that leads to the activation of IKKα/β kinase, which in turn enables the NF-κB transcription factor phosphorylation and translocation in the cell nucleus, and induction of IkB and WIP1 (as an example of induced protein that promotes NF-κB dephosphorylation 2) gene transcription. Models were based on the current knowledge of TLR signaling framework, protein interactions within the TLR4 pathway, and up-to-date mathematical models describing Toll receptor activation.
The major important additions were made to TLR4 signaling description:
1) Receptor dimerization process
2) The existence of a basal nuclear NF-κB level (translocation)
3) NF-κB phosphorylation by IKK complex
2019-03-27 | MODEL1809230001 | BioModels