Rugulation of TNF-mediated macrophage differentiation and function by RBP-J
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ABSTRACT:
PROVIDER: PRJNA1012806 | ENA |
REPOSITORIES: ENA
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Project description:RBP-J was initially identified as a key regulator in the canonical Notch signaling pathway. More recent studies have unveiled its important role as a significant player in macrophage polarization, TLR and TNF signaling pathways. Since TNF activates RBP-J, we investigated the transcriptomic changes in murine bone marrow macrophages treated without or with TNF.
2025-01-28 | GSE242269 | GEO
Project description:Here we explored how the human macrophage response to tumor necrosis factor (TNF) is regulated by human synovial fibroblasts, the representative stromal cell type in the synovial lining of joints that become activated during inflammatory arthritis. Genome-wide transcriptome analysis (RNAseq) showed that co-cultured synovial fibroblasts modulate the expression of approximately one third of TNF-inducible genes in macrophages, including expression of target genes in pathways important for macrophage survival and polarization towards an alternatively activated phenotype. This work furthers our understanding of the interplay between innate immune and stromal cells during an inflammatory response, one that is particularly relevant to inflammatory arthritis. Our findings also identify modulation of macrophage phenotype as a new function for synovial fibroblasts that may prove to be a contributing factor in arthritis pathogenesis. Human CD14+ MCSF-differentiated macrophages were cultured with or without synovial fibroblasts in transwell chambers. TNF was added at Day 0, macrophages were harvested at Day 2. Total of 4 samples: (1) macrophages alone (2) macrophages with fibroblasts (3) macrophages with TNF (4) macrophages with fibroblasts and TNF. Macrophage RNA was purified using RNeasy mini kit (Qiagen). Tru-seq sample preparation kits (Illumina) were used to purify poly-A transcripts and generate libraries with multiplexed barcode adaptors. All samples passed quality control on a Bioanalyzer 2100 (Agilent). Paired-end reads (50 x 2 cycles, ~75x106 reads per sample) were obtained on an Illumina HiSeq 2500. The TopHat program was used to align the reads to the UCSC Hg19 human reference genome, while the Cufflinks program allowed for measurements of transcript abundance (represented by Fragments Per Kilobase of exon model per Million mapped reads (FPKM)).
2014-08-04 | E-GEOD-57723 | biostudies-arrayexpress
Project description:TNF-mediated macrophage polarization is important for inflammatory disease pathogenesis, but mechanisms that regulate polarization are not well understood. Transcriptomic and epigenomic analysis of the TNF response in primary human macrophages revealed late phase activation of SREBP2, the master regulator of cholesterol biosynthesis genes. TNF stimulation extended the genomic profile of SREBP2 occupancy to include binding to and activation of inflammatory and interferon response genes independently of its functions in sterol metabolism. Genetic ablation of SREBP function shifted the balance of macrophage polarization from M1 to an M2-like reparative phenotype in peritonitis and skin wound healing models. Genetic ablation of SREBP activity in myeloid cells or topical pharmacological inhibition of SREBP improved skin wound healing under homeostatic and chronic inflammatory conditions. Our results identify a new function and mechanism of action for SREBP2 in augmenting TNF-induced M1 macrophage polarization and inflammation, and open therapeutic avenues for promoting wound repair.
2019-04-03 | GSE129202 | GEO
Project description:TNF-mediated macrophage polarization is important for inflammatory disease pathogenesis, but mechanisms that regulate polarization are not well understood. Transcriptomic and epigenomic analysis of the TNF response in primary human macrophages revealed late phase activation of SREBP2, the master regulator of cholesterol biosynthesis genes. TNF stimulation extended the genomic profile of SREBP2 occupancy to include binding to and activation of inflammatory and interferon response genes independently of its functions in sterol metabolism. Genetic ablation of SREBP function shifted the balance of macrophage polarization from M1 to an M2-like reparative phenotype in peritonitis and skin wound healing models. Genetic ablation of SREBP activity in myeloid cells or topical pharmacological inhibition of SREBP improved skin wound healing under homeostatic and chronic inflammatory conditions. Our results identify a new function and mechanism of action for SREBP2 in augmenting TNF-induced M1 macrophage polarization and inflammation, and open therapeutic avenues for promoting wound repair.
2019-04-03 | GSE129225 | GEO
Project description:TNF-mediated macrophage polarization is important for inflammatory disease pathogenesis, but mechanisms that regulate polarization are not well understood. Transcriptomic and epigenomic analysis of the TNF response in primary human macrophages revealed late phase activation of SREBP2, the master regulator of cholesterol biosynthesis genes. TNF stimulation extended the genomic profile of SREBP2 occupancy to include binding to and activation of inflammatory and interferon response genes independently of its functions in sterol metabolism. Genetic ablation of SREBP function shifted the balance of macrophage polarization from M1 to an M2-like reparative phenotype in peritonitis and skin wound healing models. Genetic ablation of SREBP activity in myeloid cells or topical pharmacological inhibition of SREBP improved skin wound healing under homeostatic and chronic inflammatory conditions. Our results identify a new function and mechanism of action for SREBP2 in augmenting TNF-induced M1 macrophage polarization and inflammation, and open therapeutic avenues for promoting wound repair.
2019-04-03 | GSE129210 | GEO
Project description:TNF-mediated macrophage polarization is important for inflammatory disease pathogenesis, but mechanisms that regulate polarization are not well understood. Transcriptomic and epigenomic analysis of the TNF response in primary human macrophages revealed late phase activation of SREBP2, the master regulator of cholesterol biosynthesis genes. TNF stimulation extended the genomic profile of SREBP2 occupancy to include binding to and activation of inflammatory and interferon response genes independently of its functions in sterol metabolism. Genetic ablation of SREBP function shifted the balance of macrophage polarization from M1 to an M2-like reparative phenotype in peritonitis and skin wound healing models. Genetic ablation of SREBP activity in myeloid cells or topical pharmacological inhibition of SREBP improved skin wound healing under homeostatic and chronic inflammatory conditions. Our results identify a new function and mechanism of action for SREBP2 in augmenting TNF-induced M1 macrophage polarization and inflammation, and open therapeutic avenues for promoting wound repair.
2019-04-03 | GSE129167 | GEO
Project description:Anti-TNF therapies are a core anti-inflammatory approach for chronic diseases such as rheumatoid arthritis and Crohn’s Disease. Previously, we and others found that TNF blocks the emergence and function of alternatively-activated or M2 macrophages involved in wound healing and tissue-reparative functions. Conceivably, anti-TNF drugs could mediate their protective effects in part by an altered balanced of macrophage activity. To understand the mechanistic basis of how TNF regulates tissue-reparative macrophages we used RNAseq, scRNAseq, ATACseq, time-resolved phospho-proteomics, gene-specific approaches, metabolic analysis and signaling pathway deconvolution. Our findings reveal that TNF controls tissue-reparative macrophage gene expression in a highly gene-specific way dependent on JNK signaling. We uncover principles of the selectively inhibition by TNF via the type 1 TNF receptor on specific populations of alternative activated macrophages.
2022-01-07 | PXD028667 | Pride
Project description:Here we explored how the human macrophage response to tumor necrosis factor (TNF) is regulated by human synovial fibroblasts, the representative stromal cell type in the synovial lining of joints that become activated during inflammatory arthritis. Genome-wide transcriptome analysis (RNAseq) showed that co-cultured synovial fibroblasts modulate the expression of approximately one third of TNF-inducible genes in macrophages, including expression of target genes in pathways important for macrophage survival and polarization towards an alternatively activated phenotype. This work furthers our understanding of the interplay between innate immune and stromal cells during an inflammatory response, one that is particularly relevant to inflammatory arthritis. Our findings also identify modulation of macrophage phenotype as a new function for synovial fibroblasts that may prove to be a contributing factor in arthritis pathogenesis.
2014-08-04 | GSE57723 | GEO
Project description:We sequenced microRNAs from bone marrow derived macrophages derived from the control (WT) and RBP-J conditional knockout mice (RBP-J KO; Rbpjf/f; LysM Cre). Examination of differential microRNA expression levels induced by TNF as well as regulated by RBP-J in bone marrow derived macrophages.
2016-07-22 | E-GEOD-72966 | biostudies-arrayexpress
Project description:We report that macrophage elasticity plays a dominant role in bacterial phagocytosis, release of TNF-alpha, and production of reactive oxygen species. We show that macrophage elasticity is modulated by mechanical factors including substrate rigidity and substrate stretch. Changes in macrophage elasticity are dependent upon the degree of actin polymerization, and mediated in part through small rhoGTPase activity. Moreover, the functional effects of macrophage elasticity are not predicted by gene expression profiles. Murine RAW 267.4 macrophages were separately grown on 2 matrix stiffness levels (1200, 150000 Pascals) for 0, 2, 6, 18 hours with 3 replicate sample experiments per condition. Total RNA extracted from the cells and profiled by microarrays. Keywords: Murine RAW 267.4 macrophage, matrix stiffness, phagocytosis, cell elasticity.
2012-03-28 | E-GEOD-36878 | biostudies-arrayexpress