OGT suppresses macrophage proinflammatory activation
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA607991 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR11141900_1.fastq.gz | Fastqsanger.gz | |||
| SRR11141900_2.fastq.gz | Fastqsanger.gz | |||
| SRR11141901_1.fastq.gz | Fastqsanger.gz | |||
| SRR11141901_2.fastq.gz | Fastqsanger.gz | |||
| SRR11141902_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 48 |
Similar Datasets
Project description:Overnutrition leads to metabolic disorders such as obesity and diabetes. Enhanced inflammation has also been shown to be an essential player in the progression of metabolic diseases. However, how immune cells sense nutritional status and contribute to whole-body metabolism remain largely elusive. OGT-catalyzed protein O-GlcNAcylation is thought to be a metabolic sensor that modulates cell signaling. In this study, we show that overnutrition stimulates macrophage O-GlcNAc signaling. O-GlcNAc signaling suppresses macrophage proinflammatory activation and protects against diet-induced obesity and metabolic dysfunction. These findings thus identify macrophage O-GlcNAc signaling as a novel homeostatic regulator at the interface of inflammation and metabolism.
2020-07-22 | GSE145720 | GEO
Project description:Lipin2 limits macrophage proinflammatory response.
| PRJNA701892 | ENA
Project description:Nrf2 (NF-E2-related factor-2) transcription factor regulates oxidative/xenobiotic stress response and also represses inflammation. However, the mechanisms how Nrf2 alleviates inflammation are still unclear. Here, we demonstrate that Nrf2 interferes with lipopolysaccharide-induced transcriptional upregulation of proinflammatory cytokines, including IL-6 and IL-1β. ChIP-seq and ChIP-qPCR analyses revealed that Nrf2 binds to the proximity of these genes in macrophages and inhibits RNA Pol II recruitment. Further, we found that Nrf2-mediated inhibition is independent of the Nrf2 binding motif and reactive oxygen species level. Murine inflammatory models further demonstrated that Nrf2 interferes with IL6 induction and inflammatory phenotypes in vivo. Thus, contrary to the widely accepted view that Nrf2 suppresses inflammation through redox control, we demonstrate here that Nrf2 opposes transcriptional upregulation of proinflammatory cytokine genes. This study identifies Nrf2 as the upstream regulator of cytokine production and establishes a molecular basis for an Nrf2-mediated anti-inflammation approach. Gene expression in BMDMs obtained from wild-type and Keap1-CKO mice. In Keap1-CKO (Keap1 flox/flox::LysM-Cre) BMDMs, Nrf2 transcription factor is activated due to Keap1-deficiency. BMDMs were obtained by a culture of bone marrow cells in the presence of M-CSF for7 days. M1-activated BMDMs were obtained by stimulation with LPS and IFNg for 6 hours, while M2-activated BMDMs were obtained by a stimulation with IL-4 for 6 hours. Two independent BMDM cultures were performed, and each experiment contains samples obtained from one wild-type and one Keap1-CKO mice, respectively.
2016-05-12 | E-GEOD-71263 | biostudies-arrayexpress
Project description:Nrf2 (NF-E2-related factor-2) transcription factor regulates oxidative/xenobiotic stress response and also represses inflammation. However, the mechanisms how Nrf2 alleviates inflammation are still unclear. Here, we demonstrate that Nrf2 interferes with lipopolysaccharide-induced transcriptional upregulation of proinflammatory cytokines, including IL-6 and IL-1β. ChIP-seq and ChIP-qPCR analyses revealed that Nrf2 binds to the proximity of these genes in macrophages and inhibits RNA Pol II recruitment. Further, we found that Nrf2-mediated inhibition is independent of the Nrf2 binding motif and reactive oxygen species level. Murine inflammatory models further demonstrated that Nrf2 interferes with IL6 induction and inflammatory phenotypes in vivo. Thus, contrary to the widely accepted view that Nrf2 suppresses inflammation through redox control, we demonstrate here that Nrf2 opposes transcriptional upregulation of proinflammatory cytokine genes. This study identifies Nrf2 as the upstream regulator of cytokine production and establishes a molecular basis for an Nrf2-mediated anti-inflammation approach.
2016-05-12 | GSE71263 | GEO
Project description:TET2 directly interacts with OGT, which is important for the chromatin association of OGT in vivo. Although this specific interaction does not regulate the enzymatic activity of TET2, it facilitates OGT-dependent histone O-GlcNAcylation. Moreover, OGT associates with TET2 at transcription starting sites (TSS). Down-regulation of TET2 reduces the amount of H2B S112 GlcNAc marks in vivo, which are associated with gene transcription regulation. We found that OGT interacts with TET2 tightly. Using ChIP-seq with specific antibodies, we tested the co-localization of TET2 and OGT in genome level.
2012-12-11 | E-GEOD-41720 | biostudies-arrayexpress
Project description:Enhanced inflammation is believed to contribute to overnutrition-induced metabolic disturbance. Nutrient flux has also been shown to be essential for immune cell activation. Here, we report an unexpected role of nutrient-sensing O-linked ?-N-acetylglucosamine (O-GlcNAc) signaling in suppressing macrophage proinflammatory activation and preventing diet-induced metabolic dysfunction. Overnutrition stimulates an increase in O-GlcNAc signaling in macrophages. O-GlcNAc signaling is down-regulated during macrophage proinflammatory activation. Suppressing O-GlcNAc signaling by O-GlcNAc transferase (OGT) knockout enhances macrophage proinflammatory polarization, promotes adipose tissue inflammation and lipolysis, increases lipid accumulation in peripheral tissues, and exacerbates tissue-specific and whole-body insulin resistance in high-fat-diet-induced obese mice. OGT inhibits macrophage proinflammatory activation by catalyzing ribosomal protein S6 kinase beta-1 (S6K1) O-GlcNAcylation and suppressing S6K1 phosphorylation and mTORC1 signaling. These findings thus identify macrophage O-GlcNAc signaling as a homeostatic mechanism maintaining whole-body metabolism under overnutrition.
| S-EPMC7368321 | biostudies-literature
Project description:Antibody responses, involving B cells, CD4+ T cells, and macrophages, are implicated in autoimmune diseases and organ transplant rejection. We have previously shown that inhibiting FROUNT with disulfiram (DSF) suppresses macrophage activation and migration, effectively treating inflammatory diseases. In this study, we investigated the effectiveness of DSF in antibody-producing reactions. Using a heart transplantation mouse model with antibody-mediated rejection, we administered anti-CD8 antibody to exclude cellular rejection. DSF directly inhibited B cell responses in vitro and significantly reduced plasma donor-specific antibodies and graft antibody deposition in vivo, resulting in prolonged survival of the heart graft. DSF also mediated various effects, including decreased macrophage infiltration and increased Foxp3+ regulatory T-cells in the grafts. Additionally, DSF inhibited pyrimidine metabolism-related gene expression induced by B-cell stimulation. These findings demonstrate that DSF modulates antibody production in the immune response complexity by regulating B-cell and macrophage responses.
2024-04-15 | GSE261712 | GEO
Project description:Emodin inhibits macrophage alernative activation
| PRJNA296569 | ENA
Project description:Complete activation of macrophage proinflammatory and antimicrobial phenotype is promoted by combined action of IFN-g and LPS. Synergistic activation of canonical inflammatory NF-kB target genes by IFN-g and LPS is well appreciated, but less is known about whether IFN-g negatively regulates components of the LPS response, and how this affects polarization. A combined transcriptomic and epigenomic approach revealed that IFN-g selectively abrogates LPS-induced feedback and select metabolic pathways by suppressing TLR4-mediated activation of gene enhancers. In contrast to superinduction of inflammatory genes via enhancers that harbor IRF sequences and bind STAT1, IFN-g-mediated repression targeted enhancers with STAT sequences that bound STAT3. TLR4-activated IFN-g-suppressed enhancers comprised two subsets distinguished by differential regulation of histone acetylation and recruitment of STAT3, CDK8 and cohesin, and were functionally inactivated by IFN-g. These findings reveal that IFN-g suppresses feedback inhibitory and metabolic components of the TLR response to achieve full macrophage activation and provide insights into mechanisms by which IFN-g selectively inhibits TLR4-induced transcription.
2019-06-12 | GSE131294 | GEO
Project description:Macrophage activation syndrome (MAS) is a life-threatening cytokine storm syndrome complicating systemic juvenile idiopathic arthritis (SJIA) and driven by IFN-gamma. SJIA and MAS are also associated with an unexplained emerging inflammatory lung disease (SJIA-LD), with our recent work supporting pulmonary activation of IFN-gamma pathways as a pathologic link between SJIA-LD and MAS. Our objective was to mechanistically define the novel observation of pulmonary inflammation in the TLR9 mouse model of MAS. In acute MAS, lungs exhibit mild but diffuse CD4-predominant, perivascular interstitial inflammation with elevated IFN-gamma, IFN-induced chemokines, and alveolar macrophage expression of IFN-gamma-induced genes. Single-cell RNA-sequencing confirmed IFN-driven transcriptional changes across immune and parenchymal lung cell types. Resolution of MAS was associated with increased alveolar macrophage and interstitial lymphocytic infiltration. alveolar macrophage microarrays confirmed IFN-gamma-induced proinflammatory polarization during acute MAS, which switches towards an anti-inflammatory phenotype during MAS resolution. Interestingly, recurrent MAS led to increased alveolar inflammation and lung injury, and reset alveolar macrophagepolarization towards a proinflammatory state. Furthermore, in mice bearing macrophages insensitive to IFN-gamma, both systemic feature of MAS and pulmonary inflammation were attenuated. These findings demonstrate that experimental MAS induces IFN-gamma-driven pulmonary inflammation replicating key features of SJIA-LD, and provides a model system for testing novel treatments directed towards SJIA-LD.
2021-09-12 | GSE169325 | GEO