Analysis of the IFNgamma induced pathways in murine macrophages
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE116364 | GEO | 2019/01/01
REPOSITORIES: GEO
Similar Datasets
Project description:Analysis of the IFNgamma induced pathways in murine macrophages
| PRJNA478256 | ENA
Project description:Gene expression profiling of macrophages derived from WT and Vdr deficient mice after stimulation with IFNgamma and/or 1alpha,25(OH)2D3 Keywords = macrophages Keywords = VDR Keywords = activated vitamin D3 Keywords = IFNgamma Keywords = KO mice Keywords: dose response
2005-04-21 | GSE2421 | GEO
Project description:To study the role of SOCS1 in the cell nucleus in vivo, we generated a transgenic mouse model using a bacterial artificial chromosome (BAC) containing a mutated Socs1 locus (non-nuclear Socs1ÎNLS), GFP and firefly Luciferase, termed MGL. MGL transgenic mice expressing only non-nuclear mutant Socs1 (Socs1-/- MGLtg mice) survive the early lethal phenotype of Socs1-/- mice that die within 3 weeks due to excessive immune signaling, mainly depending on hyperresponsiveness to IFNgamma. Therefore, we suggested that classical IFNgamma signaling might still be efficiently regulated by SOCS1ÎNLS. To prove this hypothesis, bone marrow-derived macrophages (BMMs) from Socs1-/- MGLtg mice and the control group (Socs1+/- MGLtg mice) were stimulated with IFNgamma for 24 h and subjected to whole-genome expression analysis.
2016-11-10 | E-MTAB-4938 | biostudies-arrayexpress
Project description:Macrophages derived from the wt and 1h mice were treated with the increasing concentrations of the TNF followed by the RNA-Seq analysis.
2019-01-01 | GSE115905 | GEO
Project description:Gene expression profiling of macrophages derived from WT and Vdr deficient mice after stimulation with IFNgamma and/or 1alpha,25(OH)2D3
2007-08-31 | E-GEOD-2421 | biostudies-arrayexpress
Project description:Clinical approaches to treat advanced melanoma include immune therapies, whose benefits depend on tumor-reactive T-cells to infiltrate metastases. However, most tumors lack significant immune infiltration prior to therapy, and some immune therapies are hindered by a persistent lack of immune cell infiltration. CXCL10 has been implicated as a critical chemokine supporting T-cell migration into tumors; thus agents that induce CXCL10 in tumors may improve patient responses to systemic immune therapy. We find that melanoma cells treated with TLR2/6 agonists (MALP-2 or FSL-1) and interferon-gamma (IFNgamma) upregulate CXCL10 production, when compared to IFNgamma treatment alone or no treatment. Gene profiling of melanoma cells lines treated with TLR2/6 agonists and IFNgamma demonstrate that a selective profile of genes are induced which may be favorable for promoting immune cell infiltration of tumors. TLR2 and TLR6 are widely expressed on human melanoma cells, and treatment of melanoma cells with TLR2/6 agonists and IFNgamma does not hinder melanoma cell apoptosis or promote proliferation. Furthermore, melanoma cells from surgically resected patient tumors upregulate CXCL10 production after treatment with TLR2/6 agonists and IFNgamma when compared to treatment with either agent alone. Collectively, these data identify TLR2/6 agonists and IFNgamma as a novel target for promoting CXCL10 production directly from melanoma cells.
2015-11-22 | GSE64506 | GEO
Project description:Introduction: Optimal approaches to induce T-cell infiltration of tumors are not known. Chemokines CXCL9, CXCL10, and CXCL11 support effector T-cell recruitment, and may be induced by IFNgamma. This study tests the hypothesis that intratumoral administration of IFNgamma will induce CXCL9-11, and will induce T-cell recruitment and anti-tumor immune signatures in melanoma metastases. Patients and Methods: Nine eligible patients were immunized with a vaccine comprised of 12 class I MHC-restricted melanoma peptides (12MP) and received IFNgamma intratumorally. Effects on the tumor microenvironment (TME) were evaluated in sequential tumor biopsies. Adverse events (AE; CTCAE v4) were recorded. T-cell responses to vaccination were assessed in peripheral blood (PBMC) by IFNgamma ELIspot assay. Tumor biopsies were evaluated for immune cell infiltration, chemokine protein expression and gene expression. Results: Vaccination and intratumoral administration of IFNgamma were well tolerated. Circulating T-cell responses to vaccine were detected in 6 of 9 patients. IFNgamma increased production of chemokines CXCL10, CXCL11, and CCL5 in patient tumors. Neither vaccination alone nor the addition of IFNgamma promoted immune cell infiltration or induced anti-tumor immune gene signatures. Conclusion: The cancer vaccine did not significantly increase T-cell infiltration of tumors. This study provides intriguing findings highlighting some of the limitations of intratumoral IFNgamma treatment. Although IFNgamma is pivotal in anti-tumor immunity, single intratumoral injection may induce secondary immune regulation that paradoxically limits immune infiltration and effector functions. Therefore, alternate dosing strategies or additional combinatorial treatments may be needed to optimally promote trafficking and retention of T-cells in tumor, which merit further study.
2017-03-01 | GSE79741 | GEO
Project description:Clinical approaches to treat advanced melanoma include immune therapies, whose benefits depend on tumor-reactive T-cells to infiltrate metastases. However, most tumors lack significant immune infiltration prior to therapy, and some immune therapies are hindered by a persistent lack of immune cell infiltration. CXCL10 has been implicated as a critical chemokine supporting T-cell migration into tumors; thus agents that induce CXCL10 in tumors may improve patient responses to systemic immune therapy. We find that melanoma cells treated with TLR2/6 agonists (MALP-2 or FSL-1) and interferon-gamma (IFNgamma) upregulate CXCL10 production, when compared to IFNgamma treatment alone or no treatment. Gene profiling of melanoma cells lines treated with TLR2/6 agonists and IFNgamma demonstrate that a selective profile of genes are induced which may be favorable for promoting immune cell infiltration of tumors. TLR2 and TLR6 are widely expressed on human melanoma cells, and treatment of melanoma cells with TLR2/6 agonists and IFNgamma does not hinder melanoma cell apoptosis or promote proliferation. Furthermore, melanoma cells from surgically resected patient tumors upregulate CXCL10 production after treatment with TLR2/6 agonists and IFNgamma when compared to treatment with either agent alone. Collectively, these data identify TLR2/6 agonists and IFNgamma as a novel target for promoting CXCL10 production directly from melanoma cells. Samples from four human melanoma cell lines, VMM1 (n=6), DM13 (n=6), DM93 (n=6) and VMM39 (n=6), were treated with media alone, MALP-2 (TLR2/6 agonist), FSL-1 (TLR2/6 agonist), IFNgamma alone, MALP-2 and IFNgamma, or FSL-1 and IFNgamma.
2015-11-22 | E-GEOD-64506 | biostudies-arrayexpress
Project description:The purpose of this study is to define which genes are IFNgamma sensitive, resistant, or irrelevant in our desired 16MB Human genome. Different ISGs(Interferon sensitive genes) were categorized based on this expression array data and can be visulized in our 16MB IFNgamma genes DB. Keywords: treated/untreated different time point comparison
2009-01-15 | GSE11299 | GEO
Project description:OBJECTIVE: To determine whether macrophages, a type of cell implicated in the pathogenesis of ankylosing spondylitis (AS), exhibit a characteristic gene expression pattern. METHODS: Macrophages were derived from the peripheral blood of 8 AS patients (median disease duration 13 years [range <1-43 years]) and 9 healthy control subjects over 7 days with the use of granulocyte-macrophage colony-stimulating factor. Cells were stimulated for 24 hours with interferon-gamma (IFNgamma; 100 units/ml), were left untreated for 24 hours, or were treated for 3 hours with lipopolysaccharide (LPS; 10 ng/ml). RNA was isolated and examined by microarray and real-time quantitative reverse transcription-polymerase chain reaction analysis. RESULTS: Microarray analysis revealed 198 probe sets detecting the differential expression of 141 unique genes in untreated macrophages from AS patients compared with healthy controls. Clustering and principal components analysis clearly distinguished AS patients and controls. Of the differentially expressed genes, 78 (55%) were IFN-regulated, and their relative expression indicated a reverse IFN signature in AS patient macrophages, where IFNgamma-up-regulated genes were underexpressed and down-regulated genes were overexpressed. Treatment of macrophages with exogenous IFNgamma normalized the expression of these genes between patients and controls. In addition, the messenger RNA encoded by the IFNgamma gene was approximately 2-fold lower in AS patient macrophages at baseline (P = 0.004) and was poorly responsive to LPS (P = 0.018), as compared with healthy controls. CONCLUSIONS: Our findings reveal consistent differences in gene expression in macrophages from AS patients, with evidence of a striking reverse IFN signature. Together with poor expression and responsiveness of the IFNgamma gene, these results suggest that there may be a relative defect in IFNgamma gene regulation, with autocrine consequences and implications for disease pathogenesis. Keywords: Disease state analysis with treatment effect
2008-06-27 | GSE11886 | GEO