Similar Datasets
Project description:Control of macrophage response to TNF by the sst1 locus
| PRJNA691585 | ENA
Project description:Bone marrow derived macrophages from C57BL/6 or C57BL/6-Sst1S strains of mice were pretreated ± 100U/ml interferon gamma then infected for 0, 1, 2, 4, or 6h with Listeria monocytogenes. C57BL/6-Sst1S mice carry the Sst1 chromosomal locus of C3H mice. The Sst1 locus controls susceptibility to intracellular pathogens - these mice are therefore more susceptible than wild type B6.
2017-06-30 | E-MTAB-5784 | biostudies-arrayexpress
Project description:This study reports the expression profile of intracellular B. pseudomallei following infection of human macrophage-like U937 cells. The transcriptome of intracellular B. pseudomallei harvested from macrophage cells over an infection period of 6 hr (1, 2, 4 and 6 hr post-infection) were compared to in vitro grown bacteria to identify genes whose expression is altered in response to intracellular growth. The experimental design of this study involved the total RNA from intracellular B. pseudomallei harvested from infected U937 cells at 4 selected time points with 3 biological replicates each. The microarray data from each time point was compared relative to in vitro grown bacteria in cell culture medium.
2011-12-31 | E-GEOD-27558 | biostudies-arrayexpress
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:This study reports the expression profile of intracellular B. pseudomallei following infection of human macrophage-like U937 cells. The transcriptome of intracellular B. pseudomallei harvested from macrophage cells over an infection period of 6 hr (1, 2, 4 and 6 hr post-infection) were compared to in vitro grown bacteria to identify genes whose expression is altered in response to intracellular growth.
2011-12-31 | GSE27558 | GEO
Project description:Immune checkpoint inhibitors (ICI) represent new anticancer agents and have been used worldwide. However, ICI can potentially induce life-threatening severe cutaneous adverse reaction (SCAR), such as Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), hindering continuous ICI therapy. We examined 6 cohorts within 25 ICI-induced SJS/TEN patients and conducted single-cell RNA sequencing (scRNA-seq) analysis, which revealed overexpression of macrophage-derived CXCL10 that recruited CXCR3+ cytotoxic T lymphocytes (CTL) in blister cells from ICI-SJS/TEN skin lesions. ScRNA expression profiles and ex vivo blocking studies further identified TNF signaling as the key pathway responsible for macrophage-derived CXCL10 and CTL activation. Based on the trajectory analysis, ICI-activated T cells from whole blood are proposed to serve as the initial cells involved in inflammation, that lead to monocytes differentiating into macrophages and increasing their susceptibility to migrate to the lesion sites. Compared with systemic corticosteroids treatment, ICI-induced SJS/TEN patients treated with biologic TNF blockade showed a significantly rapid recovery and no recurrence of SCAR with continuous ICI therapy. Our findings identified that macrophage-eliciting CTL contribute the pathogenesis of ICI-induced epidermal necrolysis and provide the therapeutic targets for the management and prevention of SCAR induced by ICI therapy.
2024-08-26 | GSE273720 | GEO
Project description:The pro-inflammatory cytokine, tumor necrosis factor-alpha (TNF-α), has been suggested to be a key factor in the induction of obesity-associated metabolic dysfunction. However, the role that macrophage-derived TNF-α has on regulating metabolic perturbations in obesity is not completely understood. Therefore, we utilized the TNF-αFlox/FLox (F/F), LyzMcre+/- mouse model to determine the impact that macrophage TNF-α deletion has on the development of high-fat-diet (HFD)-induced obesity.
2021-10-01 | GSE171267 | 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 | GSE129202 | GEO