Mus musculus
Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: E-GEOD-43075
PROVIDER: PRJNA184347 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Monocyte chemoattractant protein 1 (MCP-1/CCL2) is critically involved in directing the migration of blood monocytes to sites of inflammation. Consequently, excessive MCP-1 secretion has been linked to many (auto)inflammatory diseases, whereas a lack of expression severely impairs immune responsiveness. We demonstrate that the atypical inhibitor of NF-κB ζ (IκBζ), a transcriptional co-activator required for the selective expression of a subset of NF-κB target genes, is a key activator of the Ccl2 gene. IκBζ-deficient macrophages exhibited impaired secretion of MCP-1 when challenged with diverse inflammatory stimuli, such as lipopolysaccharide or peptidoglycan. These findings were reflected at the level of Ccl2 gene expression, which was tightly coupled to the presence of IκBζ. Moreover, mechanistic insights acquired by chromatin immunoprecipitation demonstrate that IκBζ is directly recruited to the proximal promoter region of the Ccl2 gene and required for histone H3K9 trimethylation. Finally, IκBζ-deficient mice showed significantly impaired MCP-1 secretion and monocyte infiltration in an experimental model of peritonitis. Together, these findings suggest a distinguished role of IκBζ in mediating the targeted recruitment of monocytes in response to local inflammatory events. Peritoneal macrophages from Wildtype and IκBζ-Knockout mice were either stimulated with 1µg/ml LPS for 4h or left untreated (triplicates each)
2013-04-09 | E-GEOD-43075 | biostudies-arrayexpress
Project description:Monocyte chemoattractant protein 1 (MCP-1/CCL2) is critically involved in directing the migration of blood monocytes to sites of inflammation. Consequently, excessive MCP-1 secretion has been linked to many (auto)inflammatory diseases, whereas a lack of expression severely impairs immune responsiveness. We demonstrate that the atypical inhibitor of NF-κB ζ (IκBζ), a transcriptional co-activator required for the selective expression of a subset of NF-κB target genes, is a key activator of the Ccl2 gene. IκBζ-deficient macrophages exhibited impaired secretion of MCP-1 when challenged with diverse inflammatory stimuli, such as lipopolysaccharide or peptidoglycan. These findings were reflected at the level of Ccl2 gene expression, which was tightly coupled to the presence of IκBζ. Moreover, mechanistic insights acquired by chromatin immunoprecipitation demonstrate that IκBζ is directly recruited to the proximal promoter region of the Ccl2 gene and required for histone H3K9 trimethylation. Finally, IκBζ-deficient mice showed significantly impaired MCP-1 secretion and monocyte infiltration in an experimental model of peritonitis. Together, these findings suggest a distinguished role of IκBζ in mediating the targeted recruitment of monocytes in response to local inflammatory events.
2013-04-09 | GSE43075 | GEO
Project description:Inhibitor of NFκB ζ (IκBζ) is a transcriptional key regulator of monocyte chemoattractant protein-1 (MCP-1/CCL2)
2015-07-08 | E-GEOD-43075 | ExpressionAtlas
Project description:Enforced enhancement of H3K4me3 and H3K27ac, active chromatin marks, by inhibiting histone demethylases and deacetylases is positively linked with hard tissue formation by inducing matrix synthesis and osteo/odontogenic differentiation. However, the key endogenous epigenetic modifier of odontoblasts to regulate the expression of the genes coding dentin extracellular matrix (ECM) proteins has not been identified yet. We herein focused on IκBζ, which was originally identified as transcriptional regulator for NF-B and recently regarded as the local epigenetic modifier by independently on NF-B, and demonstrated that the IκBζ null mice exhibited thicker dentin width and narrower pulp chamber with aged mice having more drastic phenotypes. At 6 months old, dentin fluorescent labeling exhibited that dentin synthesis was significantly accelerated in the incisors of IκBζ null mice. In molars of IκBζ null mice, aggressive reactionary dentin adjacent to pulp horn was exhibited. Mechanistically, COL1A2 and COL1A1 collagen genes were increased in the odontoblasts rich fraction of IκBζ null mice than that of wild type in vivo and human odontoblasts-like cells transfected with siRNA for IκBζ than the control siRNA transfected cells in vitro. Further, the direct binding of IκBζ to COL1A2 promoter suppressed COL1A2 expression and the local active chromatin status marked with H3K4me3. By whole-genomic identification of H3K4me3 enrichments revealed that ECM and ECM organization-related gene loci were selectively activated by the knockdown of IκBζ, which consistently resulted in the up-regulation of these genes. Collectively, these results indicated that IκBζ is the key negative regulator of dentin formation in odontoblasts since the deletion of IκBζ expression enhanced dentin formation by inducing dentin ECM and ECM organization-related gene expression via altering the local chromatin status marked by H3K4me3. Therefore, IκBζ is a potential target for improving the clinical outcomes of dentin regeneration therapies such as pulp capping and pulp revitalization procedures.
2022-03-31 | GSE181596 | GEO
Project description:Purpose: To investigate the effects of T cell-derived cytokines on gene and protein expression of chemokines in a human RPE cell line (ARPE-19). Methods: We used an in vitro co-culture system in which the RPE and CD3/28-activated T cells were separated by a membrane. Differential gene expression in the RPE cells of chemokine genes was quantified using three different microarrays. Protein expression was determined by single- and multiplex ELISA and immunoblotting. Results: Co-culture with activated T cells increased RPE mRNA and protein expression of chemokines CCL2 (MCP-1), CCL5 (RANTES), CCL7 (MCP-3), CCL8 (MCP-2), CXCL1 (GRO-α), IL8 (CXCL8), CXCL9 (MIG), CXCL10 (IP10), CXCL11 (ITAC), and CX3CL1 (fractalkine). The secretion of CCL7 and CXCL9, 10, and 11 was polarized in the apical direction. Using recombinant human cytokines and neutralizing antibodies we identified IFNgamma and TNFalpha as the two major T cell-derived cytokines responsible for the RPE response. For CCL5, CXCL9, 10, 11, 16, and CX3CL1 we observed a synergistic effect of IFNgamma and TNFalpha in combination. CCL20, CXCL1 and 6, and IL8 were negatively regulated by IFNgamma. Conclusions: RPE cells responded to exposure to T cell-derived cytokines by upregulating expression of several chemokines related to microglial, T cell, and monocyte chemotaxis and activation. This inflammatory stress response may have implications for immune homeostasis in the retina, and for the further understanding of inflammatory ocular diseases such as uveitis and age-related macular degeneration. Differentiated ARPE19 grown on inserts in serum-free media was basolaterally stimulated for 48h with activated T cells or recombinant cytokines (IFNg and/or TNFa) or neutralizing antibodies (aIFNg and/or aTNFa)
2012-11-19 | E-GEOD-36331 | biostudies-arrayexpress
Project description:Myeloid cells comprise the majority of immune cells in tumors, where their content and composition is not only driver mutation-specific, but also tumor type-dependent. While these cells are essential for shaping the tumor microenvironment, promoting tumor growth, and contributing to therapeutic resistance, targeting tumor-associated myeloid cells, including bone-marrow-derived monocytes and neutrophils, has not been successful. To eliminate monocyte recruitment, we employed CRISPR/Cas9-based methods to delete the region on murine chromosome 11 harboring the monocyte chemoattractant protein family (MCP) genes, Ccl2, Ccl7, Ccl8, Ccl12, and Ccl11, which we termed qMCP-KO. Using these qMCP-knockout mice in combination with genetically engineered mouse models (GEMM) of glioblastoma (GBM), we investigated myeloid infiltraion by sc-RNA seq. We found that when monocyte infiltraion was abolisehd, a compensatory influx of nuetrophil in these tumor occured. These neutrophil promote tumor growth by releasing TNF, contributing to tumor hypoxic responses and aggression.
2023-02-18 | GSE203154 | GEO
Project description:We found that 18-week administration of a prolyl hydroxylase inhibitor, enarodustat, improved glucose/lipid metabolism of BTBR ob/ob mice, which is a model of obesity and type 2 diabetes mellitus. Enarodustat-treated mice also exhibited reduced albuminuria along with ameliorated glomerular epithelial and endothelial damage. In order to elucidate the mechanism of renoprotection, we performed microarray gene expression analysis of isolated glomeruli. The initial screening process revealed 8965 probes whose absolute values of log2 (BTBR ob/ob mice treated with enarodustat/BTBR ob/ob mice treated with vehicle-only) exceeded 0.5. We then compared the expression levels of those 8965 probes between BTBR ob/ob and wild-type mice to identify molecules that were likely to be involved in the pathogenesis of glomerular injury. Such analysis revealed 71 genes which were significantly up-regulated and 47 genes which were significantly down-regulated in BTBR ob/ob mice compared to wild-type mice. The genes were ranked according to their fold-change values, and the analysis presented Ccl2/Mcp1 as the second-most up-regulated gene in BTBR ob/ob mice. The expression level of Ccl2/Mcp1 increased by 24.42-fold in BTBR ob/ob compared to wild-type mice, and its expression in enarodustat-treated BTBR ob/ob mice was decreased to 0.62 of the vehicle-only treated BTBR ob/ob mice. Urinary CCL2/MCP-1 was indeed decreased in enarodustat-treated BTBR ob/ob mice. In vitro experiments also showed that enarodustat suppressed palmitate-induced CCL2/MCP-1 production in murine mesangial cells. Taken together, enarodustat is likely to confer renoprotection through regulating the expression of CCL2/MCP-1 in the glomerulus.
2020-04-17 | GSE131266 | GEO
Project description:Extracellular ATP and PGE2 are two cAMP-elevating agents inducing semi-maturation of human monocyte-derived dendritic cells (MoDCs). We have extensively compared the gene expression profiles induced by ATPγS and PGE2 in human MoDCs using microarray technology. At 6 h of stimulation, ATPγS initiated an impressive expression profile compared to that of PGE2 (1125 genes compared to 133 genes respectively) but after 24 h, the number of genes regulated by ATPγS or PGE2 was more comparable. Many target genes involved in inflammation have been identified and validated by quantitative RT-PCR experiments. We have then focused on novel ATPγS and PGE2 target genes in MoDCs including colony-stimulating factor-1 (CSF-1), MCP-4/CCL13 chemokine, vascular endothelial growth factor (VEGF-A) and neuropilin-1 (NRP-1). ATPγS strongly down-regulated CSF-1 receptor mRNA and CSF-1 secretion which are involved in monocyte and DC differentiation. Additionally, ATPγS down-regulated several chemokines involved in monocyte and DC migration including CCL2/MCP-1, CCL3/MIP-1alpha, CCL4/MIP-1beta, CCL8/MCP-2 and CCL13/MCP-4. Interestingly, VEGF-A – a major angiogenic factor displaying immunosuppressive properties - was secreted by MoDCs in response to ATPγS, ATP or PGE2, alone or in synergy with LPS. Finally flow cytometry experiments have demonstrated that ATPγS, ATP and PGE2 down-regulate NRP-1, a receptor playing inter alia an important role in the activation of T lymphocytes by DCs. Our data give an extensive overview of the genes regulated by ATPγS and PGE2 in MoDCs and an important insight into the therapeutic potential of ATP- and PGE2-treated human DCs. Keywords: Time course, treatment comparison
2008-03-01 | GSE8539 | GEO
Project description:Purpose: To investigate the effects of T cell-derived cytokines on gene and protein expression of chemokines in a human RPE cell line (ARPE-19). Methods: We used an in vitro co-culture system in which the RPE and CD3/28-activated T cells were separated by a membrane. Differential gene expression in the RPE cells of chemokine genes was quantified using three different microarrays. Protein expression was determined by single- and multiplex ELISA and immunoblotting. Results: Co-culture with activated T cells increased RPE mRNA and protein expression of chemokines CCL2 (MCP-1), CCL5 (RANTES), CCL7 (MCP-3), CCL8 (MCP-2), CXCL1 (GRO-α), IL8 (CXCL8), CXCL9 (MIG), CXCL10 (IP10), CXCL11 (ITAC), and CX3CL1 (fractalkine). The secretion of CCL7 and CXCL9, 10, and 11 was polarized in the apical direction. Using recombinant human cytokines and neutralizing antibodies we identified IFNgamma and TNFalpha as the two major T cell-derived cytokines responsible for the RPE response. For CCL5, CXCL9, 10, 11, 16, and CX3CL1 we observed a synergistic effect of IFNgamma and TNFalpha in combination. CCL20, CXCL1 and 6, and IL8 were negatively regulated by IFNgamma. Conclusions: RPE cells responded to exposure to T cell-derived cytokines by upregulating expression of several chemokines related to microglial, T cell, and monocyte chemotaxis and activation. This inflammatory stress response may have implications for immune homeostasis in the retina, and for the further understanding of inflammatory ocular diseases such as uveitis and age-related macular degeneration.
2012-11-19 | GSE36331 | GEO
Project description:In addition to lipid second messengers derived from the plasma membrane, increasing evidence supports the existence of nuclear lipid-dependent signaling networks. Diacylglycerol is a key second messenger, generated at the nuclear level, which is metabolized by diacylglycerol kinases (DGKs). It has been demonstrated that nuclear DGK-ζ negatively regulates cell cycle progression. The aim of this study was to identify key determinants of nuclear DGK-ζ-dependent cell cycle arrest in C2C12 mouse myoblasts. Using DNA microarrays, Real-Time RT-PCR and western blot, we demonstrated that nuclear DGK-ζ downregulated the expression of cyclin D1 and increased the expression of TIS21/BTG2/PC3, a transcriptional regulator of cyclin D1 with a strong anti-proliferative function. Overexpression of TIS21/BTG2/PC3 blocked the cells in G1 phase of the cell cycle and decreased the levels of Ser807/811 phosphorylated retinoblastoma protein, similarly to overexpression of DGK-ζ. Moreover, during myogenic differentiation of C2C12 cells, we showed an increase of TIS21/BTG2/PC3 expression and a decrease in cyclin D1 levels. siRNA downregulation of TIS21/BTG2/PC3 impaired myogenic differentiation by opposing cell cycle arrest. In summary, these data identify TIS21/BTG2/PC3 and cyclin D1 as downstream effectors of the nuclear DGK-ζ and highlight the importance of this DGK isoform in the regulation of myoblast proliferation and differentiation.
2009-09-30 | GSE11770 | GEO