Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA278007 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR1910730.fastq.gz | Fastqsanger.gz | |||
| SRR1910723.fastq.gz | Fastqsanger.gz | |||
| SRR1910724.fastq.gz | Fastqsanger.gz | |||
| SRR1910725.fastq.gz | Fastqsanger.gz | |||
| SRR1910726.fastq.gz | Fastqsanger.gz |
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Project description:IFN-g Regulates mTORC1, Cellular Metabolism and mRNA Translation to Potentiate Inflammatory Macrophage Activation [RNA-Seq]
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Project description:IFN-g primes macrophages for enhanced inflammatory activation by TLRs and microbial killing, but little is known about the regulation of cell metabolism or mRNA translation during priming. We found that IFN-g regulates macrophage metabolism and translation in an integrated manner by targeting mTORC1 and MNK pathways that converge on the selective regulator of translation initiation eIF4E. Physiological downregulation of the central metabolic regulator mTORC1 by IFN-g was associated with autophagy and translational suppression of repressors of inflammation such as HES1. Genome-wide ribosome profiling in TLR2-stimulated macrophages revealed that IFN-g selectively modulates the macrophage translatome to promote inflammation, further reprogram metabolic pathways, and modulate protein synthesis. These results add IFN-g-mediated metabolic reprogramming and translational regulation as key components of classical inflammatory macrophage activation. RPF and RNAseq libraries were generated from mock or IFN-g-primed human macrophages. Cells were stimulated with Pam3Cys and harvested at 4 hours. Libraries were generated using protocol modified from Illumina Truseq technology.
2015-06-29 | E-GEOD-66809 | biostudies-arrayexpress
Project description:IFN-g primes macrophages for enhanced inflammatory activation by TLRs and microbial killing, but little is known about the regulation of cell metabolism or mRNA translation during priming. We found that IFN-g regulates macrophage metabolism and translation in an integrated manner by targeting mTORC1 and MNK pathways that converge on the selective regulator of translation initiation eIF4E. Physiological downregulation of the central metabolic regulator mTORC1 by IFN-g was associated with autophagy and translational suppression of repressors of inflammation such as HES1. Genome-wide ribosome profiling in TLR2-stimulated macrophages revealed that IFN-g selectively modulates the macrophage translatome to promote inflammation, further reprogram metabolic pathways, and modulate protein synthesis. These results add IFN-g-mediated metabolic reprogramming and translational regulation as key components of classical inflammatory macrophage activation. microRNA-seq libraries were generated from mock or IFN-g-primed human macrophages. Cells were stimulated with or without Pam3Cys and harvested at 4 hours Libraries were generated using Illumina Truseq small RNA technology.
2015-06-29 | E-GEOD-66808 | biostudies-arrayexpress
Project description:IFN-g primes macrophages for enhanced inflammatory activation by TLRs and microbial killing, but little is known about the regulation of cell metabolism or mRNA translation during priming. We found that IFN-g regulates macrophage metabolism and translation in an integrated manner by targeting mTORC1 and MNK pathways that converge on the selective regulator of translation initiation eIF4E. Physiological downregulation of the central metabolic regulator mTORC1 by IFN-g was associated with autophagy and translational suppression of repressors of inflammation such as HES1. Genome-wide ribosome profiling in TLR2-stimulated macrophages revealed that IFN-g selectively modulates the macrophage translatome to promote inflammation, further reprogram metabolic pathways, and modulate protein synthesis. These results add IFN-g-mediated metabolic reprogramming and translational regulation as key components of classical inflammatory macrophage activation.
2015-06-29 | GSE66808 | GEO
Project description:IFN-g primes macrophages for enhanced inflammatory activation by TLRs and microbial killing, but little is known about the regulation of cell metabolism or mRNA translation during priming. We found that IFN-g regulates macrophage metabolism and translation in an integrated manner by targeting mTORC1 and MNK pathways that converge on the selective regulator of translation initiation eIF4E. Physiological downregulation of the central metabolic regulator mTORC1 by IFN-g was associated with autophagy and translational suppression of repressors of inflammation such as HES1. Genome-wide ribosome profiling in TLR2-stimulated macrophages revealed that IFN-g selectively modulates the macrophage translatome to promote inflammation, further reprogram metabolic pathways, and modulate protein synthesis. These results add IFN-g-mediated metabolic reprogramming and translational regulation as key components of classical inflammatory macrophage activation.
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Project description:Macrophages are major effector cells and antigen presenting cells of the innate immune system and classical activation of macrophage function requires interferon–γ (IFN-γ) pretreatment (priming) and TLR stimuli, which promotes inflammatory responses though high levels of pro-inflammatory cytokines and lower level of the anti-inflammatory cytokines, resulting in microbicidal and tumoricidal effect. However, the underlying molecular mechanism of IFN-γ priming remains elusive. In this study, we explored the effect of IFN-γ on macrophages at miRNA level and discovered that miR-3473b, which was down-regulated after IFN-γ priming, could attenuate the priming effect of IFN-γ. Molecular study revealed that miR-3473b promoted Akt/GSK3 signaling and IL-10 production through directly targeting PTEN to suppress inflammatory response and tumor-suppressing capability of macrophages. In summary, our data demonstrate that IFN-γ beef up macrophage inflammatory response and tumor suppressing capacity by limiting miR-3473b-mediated PTEN suppression. Our work identified an IFN-γ/miR-3473b/Akt axis in the regulation of macrophage function and activation. the assay was performed with 5 μg total RNA samples from both normal BMM (labeled by Cy3) and BMM primed by IFN-γ (100U/ml) for 4 h(labeled by Cy5), normal BMM serves as control.
2014-10-01 | E-GEOD-50569 | biostudies-arrayexpress
Project description:Macrophages are major effector cells and antigen presenting cells of the innate immune system and classical activation of macrophage function requires interferon–γ (IFN-γ) pretreatment (priming) and TLR stimuli, which promotes inflammatory responses though high levels of pro-inflammatory cytokines and lower level of the anti-inflammatory cytokines, resulting in microbicidal and tumoricidal effect. However, the underlying molecular mechanism of IFN-γ priming remains elusive. In this study, we explored the effect of IFN-γ on macrophages at miRNA level and discovered that miR-3473b, which was down-regulated after IFN-γ priming, could attenuate the priming effect of IFN-γ. Molecular study revealed that miR-3473b promoted Akt/GSK3 signaling and IL-10 production through directly targeting PTEN to suppress inflammatory response and tumor-suppressing capability of macrophages. In summary, our data demonstrate that IFN-γ beef up macrophage inflammatory response and tumor suppressing capacity by limiting miR-3473b-mediated PTEN suppression. Our work identified an IFN-γ/miR-3473b/Akt axis in the regulation of macrophage function and activation.
2014-10-01 | GSE50569 | GEO
Project description:Activation of immune cells is accompanied by a metabolic reconfiguration of their cellular energy metabolism including shifts in glycolysis and mitochondrial respiration that critically regulate functional effector responses. However, while current mass spectrometry strategies identify overall or flux-dependent metabolite profiles of cells or tissues, they fail to comprehensively identify the checkpoint nodes and enzymes that are responsible for different metabolic outputs. Here, we demonstrate that a data-driven inverse modelling approach from mass spectrometry metabolomics data can be used to identify a causal biochemical node that influence overall metabolic profiles and reactions. In our study we applied this strategy to TSC2/mTORC1-dependent macrophage polarization. Using multiomics metabolomics, proteomics and transcriptomics analysis as well as enzymatic activity measurements we demonstrate that TSC2, a negative regulator of mTORC1 signaling, critically influences the cellular metabolism of macrophages by regulating the enzyme phosphoglycerate dehydrogenase (PHGDH), a rate-limiting enzyme that diverts carbon from glycolysis for de novo serine/glycine biosynthesis. This is the first evidence that the metabolic kinase mTORC1 positively regulates PHGDH activity in macrophages. Importantly, PHGDH itself is a central regulator of macrophage polarization. Anti-inflammatory (M2) macrophages have high PHGDH activity that is required for the expression of typical anti-inflammatory molecules. Inhibition of PHGDH activity suppressed marker genes in IL-4 stimulated M2 macrophages. This identifies PHGDH as a metabolic signature of M2 macrophages. The presented concept of data-driven inverse modelling and multiomics analysis allows for the systematic integration of genome-scale metabolic reconstruction, prediction and analysis of causal biochemical regulation.
2020-05-26 | PXD010657 | Pride
Project description:A hallmark of immune-inflammatory responses is the generation of reactive oxygen and nitrogen species by innate immune cells, in particular macrophages. How macrophages cope with excess oxidant production and associated redox stress is not fully understood. Recent evidence implicates reactive sulfur species (RSS) in inflammatory responses, however, how RSS affect macrophage function and its ability to cope with oxidative-inflammatory stress remains poorly understood. Herein, we investigated endogenous pathways of RSS biogenesis and clearance in macrophages, and in particular, explored how hydrogen sulfide (H2S) and thiol persulidation influences macrophage oxidative-inflammatory response. We report that classical activation of mouse or human macrophages with lipopolysaccharide and interferon-γ (LPS/IFN-γ) triggers a marked production of H2S/RSS, leading to a widespread increase in protein persulfidation. Endogenous H2S/persulfidation levels were governed by the activity of the cystine importer xCT, the H2S-generating enzyme cystathionine γ-lyase and the sulfide-metabolizing enzyme sulfide quinone oxidoreductase (SQOR). High levels of H2S/persulfidation, observed upon LPS/IFN-γ stimulation or SQOR inhibition, were associated with a state of increased resistance to oxidative stress. Furthermore, enhanced persulfidation correlated with attenuated activation of the macrophage inflammasome and diminished inflammatory cell death. These findings shed light on the metabolism and effects of RSS in macrophages and point to an important role for persulfides in enabling macrophages to cope with oxidative-inflammatory stress.
2024-05-21 | PXD044043 | Pride