Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA103303 | ENA |
REPOSITORIES: ENA
Similar Datasets
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:Podophyllotoxin (PPT) exhibits limited clinical utility due to its nephrotoxicity, and its underlying mechanisms remain poorly understood. This study employs the toxicological evidence chain (TEC) framework and integrated multi-omics analyses to investigate the potential involvement of the microbiota-gut-kidney (MGK) axis in PPT- induced nephrotoxicity in SD rats. Toxicity was systematically evaluated through longitudinal monitoring of body weight, general behavior, biochemical markers, intestinal barrier function, and histopathological alterations. In parallel, multi-omics analyses, encompassing microbiome, metabolomics, and transcriptomics, were conducted to delineate the mechanistic underpinnings. The results showed that PPT exposure induced pronounced renal and intestinal damage, manifesting as significant weight loss, diarrhea, elevated renal injury biomarkers, increased lipopolysaccharide (LPS) levels, and diamine oxidase (DAO), along with histopathological lesions and enhanced apoptosis in renal and colonic tissues. PPT exposure perturbed gut microbiota homeostasis, characterized by depletion of beneficial taxa (e.g., Lactobacillus) and enrichment of potentially pathogenic genera (e.g., Bacteroides and Aggregatibacter), concomitant with diminished short-chain fatty acid (SCFA) production and altered metabolite profiles in fecal, serum, and renal samples. Integrated multi- omics analysis further revealed activation of the JAK1/2-STAT3 signaling pathway, upregulation of pro-inflammatory mediators (TNF-α, IL-6, IL-1β, LPS, and TMAO), and suppression of anti-inflammatory cytokines (IL-10 and IL-4). These in vivo molecular and inflammatory patterns were partially reproduced in HK-2 cells co-cultured with fecal microbiota supernatant from PPT-treated rats. In addition, the JAK1/2 inhibitor ruxolitinib attenuated PPT-induced JAK1/2-STAT3 phosphorylation and inflammatory cytokine secretion in HK-2 cells. Correlation network analysis further identified associations between gut dysbiosis, systemic inflammation, and metabolic perturbations. Collectively, these findings support a mechanistic hypothesis that MGK- axis disruption and JAK1/2-STAT3 signaling may contribute to PPT-associated nephrotoxicity. However, in vivo interventional studies are required to establish definitive causality.
2026-06-27 | MTBLS14868 | MetaboLights
Project description:Podophyllotoxin (PPT) exhibits limited clinical utility due to its nephrotoxicity, and its underlying mechanisms remain poorly understood. This study employs the toxicological evidence chain (TEC) framework and integrated multi-omics analyses to investigate the potential involvement of the microbiota-gut-kidney (MGK) axis in PPT- induced nephrotoxicity in SD rats. Toxicity was systematically evaluated through longitudinal monitoring of body weight, general behavior, biochemical markers, intestinal barrier function, and histopathological alterations. In parallel, multi-omics analyses, encompassing microbiome, metabolomics, and transcriptomics, were conducted to delineate the mechanistic underpinnings. The results showed that PPT exposure induced pronounced renal and intestinal damage, manifesting as significant weight loss, diarrhea, elevated renal injury biomarkers, increased lipopolysaccharide (LPS) levels, and diamine oxidase (DAO), along with histopathological lesions and enhanced apoptosis in renal and colonic tissues. PPT exposure perturbed gut microbiota homeostasis, characterized by depletion of beneficial taxa (e.g., Lactobacillus) and enrichment of potentially pathogenic genera (e.g., Bacteroides and Aggregatibacter), concomitant with diminished short-chain fatty acid (SCFA) production and altered metabolite profiles in fecal, serum, and renal samples. Integrated multi- omics analysis further revealed activation of the JAK1/2-STAT3 signaling pathway, upregulation of pro-inflammatory mediators (TNF-α, IL-6, IL-1β, LPS, and TMAO), and suppression of anti-inflammatory cytokines (IL-10 and IL-4). These in vivo molecular and inflammatory patterns were partially reproduced in HK-2 cells co-cultured with fecal microbiota supernatant from PPT-treated rats. In addition, the JAK1/2 inhibitor ruxolitinib attenuated PPT-induced JAK1/2-STAT3 phosphorylation and inflammatory cytokine secretion in HK-2 cells. Correlation network analysis further identified associations between gut dysbiosis, systemic inflammation, and metabolic perturbations. Collectively, these findings support a mechanistic hypothesis that MGK- axis disruption and JAK1/2-STAT3 signaling may contribute to PPT-associated nephrotoxicity. However, in vivo interventional studies are required to establish definitive causality.
2026-06-28 | MTBLS14869 | MetaboLights