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Phenotypic skewing of tumor-associated macrophages by cooperative actions of IL-6 and IL-4 in IFN-stimulated differentiating monocytes

ABSTRACT: I IFNs promote differentiating monocytes to differentiate into tumor-associated macrophages (TAMs) and limit the I IFNs anti-tumor effects.But how macrophage polarization is shaped by complex signals in the tumor microenvironment during IFN therapies is incompletely understood. Herein, it was discovered that I IFNs could stimulate transitional monocytes to secrete interleukins IL-4 and IL-6, which interact to influence target genes expression in primary mouse bone-marrow-derived macrophages (BMDMs). To analyze the synergism mechanism, RNA seq was performed. Bone marrow derived macrophages were cultured under the 20ng/ml M-CSF for 7days, and treated with the indicated cytokine, samples were harvested for total RNAs and subjected to RNA sequencing analyses.

ORGANISM(S): Mus musculus

PROVIDER: GSE192371 | GEO | 2022/12/31

REPOSITORIES: GEO

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Genome-wide analysis of human macrophages stimulated with IL-4

Project description:This SuperSeries is composed of the following subset Series: GSE5099: Expression Data from Macrophage Maturation and Polarization Experiment GSE35433: Genome-wide analysis of human macrophages stimulated with IL-4 (20ng/ml) (Illumina) GSE35434: Genome-wide analysis of human macrophages stimulated with IL-4 (10ng/ml) (Illumina) GSE35435: Genome-wide analysis of mouse macrophages stimulated with IL-4 (bone marrow macrophages) (Affymetrix) GSE35436: Genome-wide analysis of mouse macrophages stimulated with IL-4 (Biogel and thioglycollate macrophages) (Affymetrix) Refer to individual Series

2012-09-29 | E-GEOD-35495 | biostudies-arrayexpress

The multifaceted responses of human monocytes to IFN-gamma and IL-4 are not reducible to M1/M2 polarization of Macrophages

Project description:Macrophages are known to be polarized into inflammatory (M1) and immunoregulatory (M2) cells when they are stimulated by agonists such as IFN-gamma and IL-4, respectively. If circulating monocytes may be polarized in response to T cell signals is often misguidedly deduced from macrophage results. Here the transcriptional responses of human CD14+ monocytes to IFN-gamma and IL-4 were analyzed using whole genome microarrays. A principal component analysis and hierarchical clustering showed that monocyte and macrophage responses were distinct. Monocytes stimulated with IFN-gamma and IL-4 for 6 hours exhibited some features of macrophage polarization. Indeed, when 80 genes considered as M1 and M2 genes were analyzed, we found that M1 genes were modulated in response to IFN-gamma and that M2 genes were modulated in response to IL-4. The M1 polarization of monocytes was transient because only M2 genes were modulated when monocytes were stimulated with IFN-gamma and IL-4 for 18 hours. However, the activation of monocytes by IFN-gamma and IL-4 could not be reduced to M1/M2 polarization status. Indeed, monocytes exhibited early specific signatures composed of 46 and 39 up-regulated genes in response to IFN-gamma and IL-4, respectively, and a late signature common to both molecules that consisted of 57 up-regulated genes. Taken together, these results demonstrated the extreme plasticity of human monocytes and suggested the existence of a core transcriptional termination program. Using early and late signatures might be pertinent to investigate monocyte activation in inflammatory or infectious diseases. Monocytes were stimulated with IFN-gamma (20ng/mL) or IL-4 (20ng/mL) for 6 and 18 hours or culture for 6 and 18 hours without agonist (Unstimulated samples). Monocytes-derived-macrophages (MDM) stimulated with IFN-gamma and IL-4 for 18 hours were used as controls. Each microarray is derived from a single biological sample.

2013-03-15 | E-GEOD-36537 | biostudies-arrayexpress

The immunomodulatory effects of IL-4 on monocyte-derived macrophages

Project description:To explore the effects of IL-4 on tumor-associated macrophagess, we first sorted CD14+ monocytes from peripheral blood mononuclear cells of healthy donors using magnetic-activated cell sorting and then induced their differentiation into macrophages by culture with M-CSF for 5 days. We then stimulated these macrophages with or without IL-4 (20 ng/ml) for 6 hours and examined gene expression using a cDNA microarray. IL-4 stimulated gene expression on monocyte-derived macrophages was measured at 6 hours after exposure to doses of 20 ng/ml IL-4.

2015-12-10 | E-GEOD-75829 | biostudies-arrayexpress

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Project description:To investigate the function OGT in the regulation of M2 polarization of macrophages, we established IL-4-activated bone marrow-derived macrophages (BMDMs) from mice of wild-type control or Lyz2-Cre/Loxp-mediated knockout of OGT. We then performed gene expression profiling analysis using data obtained from RNA-seq of wild-type (WT) and OGT-knockout (OGT-KO) macrophages at two time points during IL-4 (20ng/μl) sitmulation.

2022-09-08 | GSE210176 | GEO

Antagonizing IL-1β to treat GBM

Project description:Monocytes and monocyte-derived macrophages (MDM) from blood circulation infiltrate and promote glioblastoma growth by, at least partially, expressing pro-inflammatory cytokine IL-1β . Using SC-RNA seq, we analyze how IL1a and IL1b differentially contibute to tumor growth.

2023-10-13 | GSE200348 | GEO

Transcriptome of IL-19 negative and IL-19 positive macrophages.

Project description:RNA-seq analysis of LPS stimulated bone marrow-derived macrophages, derived from heterozygous Il19-tdTomato reporter mice to compare the transcritptome of IL-19/tdTomato negative with IL-19/tdTomato positive macrophages.

2017-08-07 | GSE94939 | GEO

IL-10 production and metabolic regulation in macrophages are linked by a TLR-driven CREB-mediated mechanism

Project description:IL-10 is produced by macrophages in diverse immune settings and is critical in limiting immune-mediated pathology. In helminth infections macrophages are an important source of IL-10, however the molecular mechanism underpinning production of IL-10 by these cells is poorly characterized. Here, bone marrow derived macrophages exposed to Excretory/Secretory (E/S) products released by Schistosoma mansoni cercariae rapidly produce IL-10 as a result of MyD88-mediated activation of MEK/ERK/RSK and p38. The phosphorylation of these kinases was triggered by TLR2 and TLR4 and converged on activation of the transcription factor CREB. Uptake of cercarial E/S products by phagocytosis was critical for the production of IL-10 and the activation of MAPKs and CREB, which indicates that interactions between E/S products with TLR2 and TLR4, may be occurring in endosomes. Following phosphorylation, CREB is recruited to a novel regulatory element in the Il10 promoter and is also responsible for regulating a network of genes involved in metabolic processes, such as glycolysis, the tricarboxylic acid cycle and oxidative phosphorylation. Moreover, skin resident tissue macrophages, which encounter S. mansoni E/S products during infection, are the first monocytes to produce IL-10 in vivo early after infection with S. mansoni cercariae. The early and rapid release of IL-10 by these cells has the potential to condition the dermal microenvironment encountered by immune cells recruited to this infection site. To conclude, we propose a mechanism by which CREB regulates the production of IL-10 by macrophages in the skin, but also has a major effect on their metabolic state. CREB binding sites 3 pooled samples of stimulated bone marrow macrophages

2015-07-08 | E-GEOD-64844 | biostudies-arrayexpress

The immunomodulatory effects of IL-4 on monocyte-derived macrophages

2015-12-10 | GSE75829 | GEO

Transcriptome of cytokines-polarized mouse bone marrow-derived macrophages

Project description:To understand the molecular signature of the IL-10/IL-18 polarized macrophages, we performed transcriptome analysis for mouse BMDMs polarized with PBS (Naïve), IFN-γ (classic M1 stimulator, M1, 20ng/ml), IL-4 (alternative M2 stimulator, M2, 20ng/ml), IL-10 (M10, 2000ng/ml), IL-18 (M18, 2000ng/ml) or IL-10 and IL-18 (M1018, 2000ng/ml each). These data suggest that IL-10 and IL-18 cooperatively modulate a set of gene expressions and pathway activities in macrophages and contribute to a distinct polarization state.

2022-06-28 | GSE178999 | GEO

Licensing of PPARg-regulated gene expression by IL-4-induced alternative macrophage activation

Project description:This SuperSeries is composed of the following subset Series: GSE16385: Expression data from human macrophages GSE16386: Expression data from human alternatively activated macrophages GSE25088: PPARg and IL-4-induced gene expression data from wild-type and STAT6 knockout mouse bone marrow-derived macrophages GSE25123: PPARg and IL-4-induced gene expression data from PPARg +/- LysCre and PPARg fl/- LysCre mouse bone marrow-derived macrophages GSE25125: PPARg and IL-4-induced gene expression data from PPARg +/- LysCre and PPARg fl/- LysCre mouse bone marrow-derived alternatively activated macrophages and immature dendritic cells (iDCs) Refer to individual Series

2010-11-18 | E-GEOD-16387 | biostudies-arrayexpress

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