Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA103303 | ENA |
REPOSITORIES: ENA
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Project description:IL-10 regulates anti-inflammatory signaling via the activation of STAT3, which in turn controls the induction of a gene expression program whose products execute inhibitory effects on pro-inflammatory mediator production. Here we show that IL-10 induces the expression of an ETS family transcriptional repressor, ETV3 and a helicase family co-repressor, SBNO2 (Strawberry notch homolog 2) in mouse and human macrophages. IL-10-mediated induction of ETV3 and SBNO2 expression was dependent upon both STAT3, and co-stimulus through the TLR pathway. We also observed that ETV3 expression was strongly induced by the STAT3 pathway induced by IL-10 but not STAT3 signaling activated by IL-6, which cannot activate the anti-inflammatory signaling pathway. ETV3 and SBNO2 specifically repressed NF-kB-mediated transcription and can physically interact. Collectively our data suggest that ETV3 and SBNO2 are components of the pathways that contribute to the downstream anti-inflammatory effects of IL-10. We compared expression profiles of macrophages isolated from IL-10 -/- mice. Macrophages were treated with either LPS or LPS plus IL-10. Treatment times were 10, 20 and 30 minutes. Experiment Overall Design: Mouse IL-10 -/- macrophages were isolated and purified and set up in culture medium containing LPS or LPS plus IL-10. A total of 18 samples were analyzed. This set contains three replicates of each treatment condition where treatment (LPS versus LPS plus IL-10) and time (10min, 20min and 30min) were varied.
2008-06-16 | E-GEOD-9509 | biostudies-arrayexpress
Project description:IL-10 regulates anti-inflammatory signaling via the activation of STAT3, which in turn controls the induction of a gene expression program whose products execute inhibitory effects on pro-inflammatory mediator production. Here we show that IL-10 induces the expression of an ETS family transcriptional repressor, ETV3 and a helicase family co-repressor, SBNO2 (Strawberry notch homolog 2) in mouse and human macrophages. IL-10-mediated induction of ETV3 and SBNO2 expression was dependent upon both STAT3, and co-stimulus through the TLR pathway. We also observed that ETV3 expression was strongly induced by the STAT3 pathway induced by IL-10 but not STAT3 signaling activated by IL-6, which cannot activate the anti-inflammatory signaling pathway. ETV3 and SBNO2 specifically repressed NF-kB-mediated transcription and can physically interact. Collectively our data suggest that ETV3 and SBNO2 are components of the pathways that contribute to the downstream anti-inflammatory effects of IL-10. We compared expression profiles of macrophages isolated from IL-10 -/- mice. Macrophages were treated with either LPS or LPS plus IL-10. Treatment times were 10, 20 and 30 minutes. Keywords: time-course, treatment response, gene expression analysis
2007-12-01 | GSE9509 | GEO
Project description:Celecoxib is recognized to have chemopreventive and anti-cancer property beyond its anti-inflammatory function. Celelcoxib treatment in AGS cells down regulates Wnt/β-catenin, STAT3, RXR and ERK/MAPK signaling pathways. Transcriptional profiling after celecoxib shows differential regulation of oncogenic pathway regulated genes.
2014-04-01 | GSE54657 | GEO
Project description:Celecoxib is recognized to have chemopreventive and anti-cancer property beyond its anti-inflammatory function. Celelcoxib treatment in AGS cells down regulates Wnt/M-NM-2-catenin, STAT3, RXR and ERK/MAPK signaling pathways. Transcriptional profiling after celecoxib shows differential regulation of oncogenic pathway regulated genes. AGS cell were treated with celecoxib in triplicates and incubated for 24 hours. The processed samples were hybridized in M-bM-^@M-^\HuGene-1_0-stM-bM-^@M-^] array and the differentially expressed genes were taken for pathway analysis and transcription factor enrichment analysis.
2014-04-01 | E-GEOD-54657 | biostudies-arrayexpress
Project description:Intrahepatic cholestasis (IC) is a common symptom of liver diseases but with limited treatment. Huangqi decoction (HQD), a classic herbal medicine, has shown protective effects against IC. In this study, the iTRAQ-based quantitative proteomics was performed to investigate the potential mechanism of HQD on alpha-naphthylisothiocyanate (ANIT) induced IC, resulting in 2,796 quantified proteins across all the samples, including 270 differentially expressed proteins under HQD treatment. Fuzzy c-means (FCM) clustering analysis of these 270 proteins revealed that the pro-inflammatory proteins, such as LCN2, SAA1, FGG, FGA, and FGB, were assigned in the Cluster 1 (up-regulated by ANIT, and down-regulated by HQD). Following functional bioinformatics analysis and protein-protein interaction (PPI) network analysis represented that these pro-inflammatory proteins were involved in the STAT3 signaling pathway. Further real-time PCR and Western blot experiments confirmed that the expression of these proteins was consistent with the proteomic results. Moreover, HQD treatment decreased the phosphorylation of STAT3 that induced by ANIT. And Western blot experiments also revealed that HQD could decrease phosphorylation of NF-κB and down-regulate the expression inflammatory genes IL-6, and therefore inhibit IL-6/STATA3 signaling pathway. In summary, the present study suggested that HQD treatment may ameliorate intrahepatic cholestasis via inhibiting the NF-κB/IL-6/STAT3 signaling pathway.
2020-01-13 | PXD014882 | Pride
Project description:The Hedgehog signaling pathway is essential for the maintenance and response of several types of stem cells. To study the transcriptional response of stem cells to HH signaling, we searched for proteins binding to GLI proteins, the transcriptional effectors of the HH pathway in mouse embryonic stem (ES) cells. We purified GLI protein complex from an ES cell line that contained a tamoxifen-inducible 3XFLAG-tagged GLI3 repressor allele by anti-FLAG immunoprecipitation and several novel GLI co-factors were identified in the complex by subsequent mass spectrometry analysis.
2016-02-04 | PXD002494 | Pride
Project description:Chronically infecting pathogens avoid clearance by the innate immune system by promoting premature transition from an initial pro-inflammatory response towards an anti-inflammatory tissue-repair response. STAT3, a central regulator of inflammation, controls this transition and thus is targeted by numerous chronic pathogens. Here we show that BepD, an effector of the chronic bacterial pathogen Bartonella henselae targeted to infected host cells, establishes an exceptional pathway for canonical STAT3 activation, thereby impairing secretion of pro-inflammatory TNF-α and stimulating secretion of anti-inflammatory IL-10. Tyrosine phosphorylation of EPIYA-related motifs in BepD facilitates STAT3 binding and activation via c-Abl-dependent phosphorylation of Y705. The tyrosine-phosphorylated scaffold of BepD thus represents a signaling hub for intrinsic STAT3 activation that is independent from canonical STAT3 activation via transmembrane receptor-associated Janus kinases. We anticipate that our findings on a molecular shortcut to STAT3 activation will inspire new treatment options for chronic infections and inflammatory diseases.
2020-02-12 | PXD017119 | Pride
Project description:Tumor-associated macrophages contribute to tumor pathogenesis and represent an attractive therapeutic target. We report that the proprotein convertase PC1/3 inhibits the TLR4 Myd88-pathway induced in macrophages by the anti-cancer agent Taxol. Thus, PC1/3 knock-down in these cells exacerbates the TLR4 MyD88-dependent pathway triggered by Taxol. In PC1/3 knock-down macrophages, Taxol drives the secretion of pro-inflammatory cytokines, inhibits STAT3 signaling and counteracts tumor-supportive activities, thus inhibiting viability, growth and invasion of glioblastoma cells. Proteomic analyses indicate that their secretomes are characterized by a unique protein profile supporting a specific paracrine anti-tumoral effect. These findings unravel the potential value of a new therapeutic strategy combining PC1/3 inhibition and activation of the TLR4 MyD88-dependent pathway to switch intra-tumoral macrophages toward an anti-tumoral immunophenotype.
2018-03-19 | PXD004444 | Pride
Project description:Mitochondrial DNA-depleted human skin fibroblasts (HSF rho0) with suppressed oxidative phosphorylation were characterized by significant changes in the expression of 2100 nuclear genes, encoding numerous protein classes, in NF-kappaB and STAT3 signaling pathways and by decreased activity of the mitochondrial death pathway, compared to the parent rho+ HSF. In contrast, the extrinsic TRAIL/TRAIL-Receptor-mediated death pathway remained highly active, and exogenous TRAIL induced higher levels of apoptosis in rho0 cells compared to rho+ HSF. Global gene expression analysis using microarray and quantitative RT-PCR demonstrated that expression levels of many growth factors and their adaptor proteins (FGF13, HGF, IGFBP4, IGFBP6, IGFL2), cytokines (IL6, IL17B, IL18, IL19, IL28B) and cytokine receptors (IL1R1, IL21R, IL31RA) were substantially decreased after mitochondrial depletion. Some of these genes were targets of NF-kappaB and STAT3, and their protein products could regulate the STAT3 signaling pathway. Alpha-irradiation induced expression of several NF-kappaB/STAT3 target genes, including IL1A, IL1B, IL6, PTGS2/COX2 and MMP12, in rho+ HSF, but this response was substantially decreased in rho0 HSF. Suppression of the IKK-NF-kappaB pathway by the small molecular inhibitor BMS-345541 and of the JAK2-STAT3 pathway by AG490 dramatically increased TRAIL-induced apoptosis in the control and irradiated rho+ HSF. Inhibitory antibodies against IL6, the main activator of JAK2-STAT3 pathway, added into the cell media, also increased TRAIL-induced apoptosis in rho+ HSF. However, NF-kappaB activation was partially lost in mitochondrial DNA-depleted HSF resulting in downregulation of the basal or radiation-induced expression of numerous NF-kappaB targets, further suppressing IL6-JAK2-STAT3, that in concert with NF-kappaB, regulated protection against TRAIL-induced apoptosis. There are 12 total samples, 3 biological replicates each of HSF rho+ and rho0 cells that were not irradiated (control=C) or irradiated (alpha=A). Cells were harvested at 4 hours after treatment.
2011-04-04 | E-GEOD-24945 | biostudies-arrayexpress