Similar Datasets
Project description:SUCNR1 signaling controls macrophage alternative activation
| PRJNA491693 | ENA
Project description:Succinate functions both as a classical TCA cycle metabolite and as an extracellular metabolic stress signal sensed by the mainly Gi-coupled succinate receptor, SUCNR1. In the present study, we characterize and compare effects and signaling pathways activated by succinate and both classes of non-metabolite SUCNR1 agonists. By use of specific receptor and pathway inhibitors, rescue in G protein depleted cells and monitoring of receptor G protein activation by BRET we surprisingly identify Gq rather than Gi signaling, to be responsible for SUCNR1-mediated effects on basic transcriptional regulation. Importantly, in primary human M2 macrophages, where SUCNR1 is highly expressed, we demonstrate that physiological concentrations of extracellular succinate act through SUCNR1 activated Gq signaling to efficiently regulate transcription of immune function genes in a manner that hyperpolarizes their M2 versus M1 phenotype. Thus, sensing of stress-induced extracellular succinate by SUCNR1 is an important transcriptional regulator in human M2 macrophages through Gq signaling.
2021-04-30 | GSE173611 | GEO
Project description:In response to microenvironmental signals macrophages undergo different activation, indicated as classic/M1 and alternative/M2 polarization. C-Myc transcription factor could be an essential player in M2 polarization. Functional relevance of c-Myc in M2 macrophage biology is investigated by evaluating the effect of 100-58F4, on the transcriptional profile induced on human macrophages by IL-4. Human monocytes were obtained from normal donor buffy coats by two-step gradient centrifugation using Ficoll (Biochrom) and Percoll (Amersham). Non-adherent cells were discarded, and the purified monocytes were incubated for 7 days in RPMI 1640 (Biochom) supplemented with 10% FCS (HyClone) and 100 ng/mL M-CSF to obtain resting macrophages. Macrophage polarization was obtained by removing the culture medium and culturing cells in RPMI 1640 supplemented with 10% FCS and 100 ng/mL LPS plus 20 ng/mL IFN-gamma (M1 polarization) or 20 ng/mL IL-4 (M2 polarization) for 24 h. When needed, chemical inhibitors were added with IL-4.
2011-09-15 | E-GEOD-32164 | biostudies-arrayexpress
Project description:In response to microenvironmental signals macrophages undergo different activation, indicated as classic/M1 and alternative/M2 polarization. C-Myc transcription factor could be an essential player in M2 polarization. Functional relevance of c-Myc in M2 macrophage biology is investigated by evaluating the effect of 100-58F4, on the transcriptional profile induced on human macrophages by IL-4.
2011-09-16 | GSE32164 | GEO
Project description:This experiment aimed at characterising the signalling pathways downstream SUCNR1 activation in murine Neural Stem Cells (NSCs). To this end, we profiled by microarray the gene expression changes induced by succinate stimulation in both wild type NSCs and GPR91-deficient NSCs.
2018-01-01 | E-MTAB-5586 | biostudies-arrayexpress
Project description:Extracellular Succinate Hyperpolarizes M2 Macrophages through SUCNR1/GPR91-Mediated Gq Signaling
| PRJNA726262 | ENA
Project description:The liver plays a crucial role in metabolic adaptations in response to nutrients, a function that is critically dependent on its zonated structure. Succinate, a key intermediate of the tricarboxylic acid cycle, has emerged as a postprandial signaling metabolite that regulates metabolic adaptations to food intake in adipose tissue and pancreatic beta cells through its receptor SUCNR1. Considering that SUCNR1 is also expressed in hepatocytes, we hypothesized a role for the succinate-SUCNR1 axis in liver metabolic homeostasis. To better understand the role of Sucnr1in hepatocytes, we generated a mouse model specifically lacking Sucnr1 in hepatocytes (Hep-Sucnr1 KO mice) and performed an RNA-seq of isolated hepatocytes from controls (Sucnr1 fl/fl mice) and Hep-Sucnr1 KO mice.
2026-04-28 | GSE301098 | GEO
Project description:GM-CSF paradoxically possesses ability to differentiate both classically activated macrophages (MØs) with dominant proinflammatory function (M1-like MØs) and alternative activated MØs with strong immunosuppressive function (M2-like MØs). The intrinsic regulatory mechanism responsible for functional polarization of MØs under GM-CSF signalling remains elusive. Here we revealed that cytokine-inducible SH2-containing protein (CIS), induced by GM-CSF, is a key determinant in controlling MØ polarization. Compared to WT MØs, Cish-/- MØs gained characteristics of alternative activated MØs (M2 MØs), showing high expression of prototypic M2 markers Arginase 1, Tgm2 and YM-1; strong suppression of T cell proliferation; and low production of IL-12 and other proinflammatory cytokines¬¬. Differing from canonical IL-4/STAT6/IRF4 signaling axis of M2 induction, development of M2 MØ characteristics in Cish-/- MØs was associated with intensified STAT5 activation and consequent IRF8 downregulation. Attenuation of GM-CSF signalling via JAK inhibition and IRF8 rescue corrected certain functional defects in Cish-/- MØs. As CIS inhibition in NK and T cells promotes anti-tumour immunity, we showed that CIS deficiency enhanced the development of intra-tumoural M2 MØs and reduced CTL induction within tumour microenvironment with elevated GM-CSF. Overall, we conclude that CIS acts as an intrinsic rheostat to control intense GM-CSF signalling in order to maintain proinflammatory functions of MØs. Targeting CIS as a checkpoint in cancer immunotherapy should consider its role in regulating myeloid cell function.
2023-01-21 | PXD018390 | Pride
Project description:Macrophages, a key cellular component of inflammation, become functionally polarized in a signal- and context-specific manner. Th2 cytokines such as IL-4 polarize macrophages to a state of alternative activation that limits inflammation and promotes wound healing. Alternative activation is mediated by a transcriptional program that is influenced by epigenomic modifications including histone acetylation. To determine if Histone Deacetylase 3 (HDAC3) has a role in macrophage polarization including alternative activation, we have performed global gene expression analysis in macrophages with and without HDAC3 and with or without IL-4 exposure. From this data, we conclude that macrophages lacking histone deacetylase 3 (HDAC3) display a polarization phenotype similar to IL-4 induced alternative activation and furthermore are hyper-responsive to IL-4 stimulation. Mouse bone marrow derived macrophages were obtained from both control and HDAC3 KO animals and treated with vehicle control (BSA) or IL-4 for 24 hours. RNA was isolated and subjected to analysis using an Agilent Whole Genome Microarray Kit.
2011-11-10 | E-GEOD-33608 | biostudies-arrayexpress
Project description:The experiments were done using an Orbitrap Fusion or an Orbitrap Fusion Lumos mass spectrometer. Multiplexing was achieved using either TMT10 or TMT11 reagents and the SPS-MS3 method. Basic pH reversed-phase chromatography (bRPLC) was used for off-line pre-fractionation; 12 fractions were analyzed for proteome mappings (PMID: 26700037) and 24 fractions plus a phosphotyrosine-enriched sample for phosphoproteome mappings (PMID: 31606085). Phosphoproteome mappings were done using both HCD fragmentation with Orbitrap fragment ion detection and CID fragmentation with ion trap fragment ion detection (PMID: 29487189, PMID: 31606085). If multiple TMT sets were required to analyze all samples from an experiment two bridge channels pooled from all samples was used to connect the data from the individual TMT sets (PMID: 28892078).
Five proteomics experiments are described in the paper:
(i) 1. Quantitative proteomics of fully polarized macrophages after 4 days of treatment with IL4 or IFNgamma/LPS to determine global proteome landscape of fully polarized THP-1-derived M1-type versus M2a-type macrophages:
Proteome mapping on Orbitrap Fusion (one TMT set)
RAW files: Marneros_4DayTreatment_proteome_fraction01 to ...fraction12
8 samples
Labeling: PMA.1 (126), PMA.2 (127n), IL4.1 (127c), IL4.2 (128n), ILJQ1.1 (128c), ILJQ1.2 (129n), IFNgamma.1 (129c), IFNgamma.2 (130n)
(ii) Time-course quantitative proteomics during the first 24 hours after induction of macrophage polarization in THP-1-derived macrophages to identify protein changes associated with M1-type (IFNgamma/LPS-induced) versus M2a-type (IL-4-induced) polarization:
Proteome mapping on Orbitrap Fusion (three TMT sets: set01, set02, set03)
RAW files:
Marneros_timecourse_proteome_TMTset01_fraction01 to ...fraction12
Marneros_timecourse_proteome_TMTset02_fraction01 to ...fraction12
Marneros_timecourse_proteome_TMTset03_fraction01 to ...fraction12
22 samples
Labeling:
set01; bridge 1 (126), PMA 0min (127n), PMA 10min (127c), PMA 30min (128n), PMA 1h (128c), PMA 2h (129n), PMA 4h (129c), PMA 8h (130n), PMA 24h (130c), bridge 2 (131n)
set02; bridge 1 (126), IL4 10min (127n), IL4 30min (127c), IL4 1h (128n), IL4 2h (128c), IL4 4h (129n), IL4 8h (129c), IL4 24h (130n), IFN 10min (130c), bridge 2 (131n)
set03; bridge 1 (126), IFN 30min (127n), IFN 1h (127c), IFN 2h (128n), IFN 4h (128c), IFN 8h (129n), IFN 24h (129c), bridge 2 (131n)
(iii) Time-course quantitative phosphoproteomics during the first 24 hours after induction of macrophage polarization in THP-1-derived macrophages to identify phosphorylation events associated with M1-type (IFNgamma/LPS-induced) versus M2a-type (IL-4-induced) polarization (same time points as in group 2):
Phosphoproteome mapping on Orbitrap Fusion (three TMT sets: set01, set02, set03)
RAW files:
Marneros_timecourse_phospho_TMTset01_fraction01 to ...fraction06, ...fraction08 to ...fraction24, ...pY
Marneros_timecourse_phospho_TMTset02_fraction01 to ...fraction12, ...fraction16 to ...fraction24, ...pY
Marneros_timecourse_phospho_TMTset03_fraction01 to ...fraction24, ...pY
The following RAW files gave no phosphopeptide quantifications (they are no included in the group of provided RAW files): set01_fraction07, set02_fraction13, set02_fraction14, set02_fraction15.
22 samples
Labeling: as in (ii)
(iv) Quantitative proteomics to assess the effects of the B-Raf inhibitor GDC-0879 or of the MEK inhibitor trametinib on IL-4-induced M2-type polarization and IFNgamma/LPS-induced M1-type polarization on THP-1-derived macrophages after 24 hours of treatment:
Proteome mapping on Orbitrap Fusion (one TMT set)
RAW files: Marneros_BRAF_inhibitor_proteine_fraction01 to ...fraction12
11 samples
Labeling: IL4 1 (131c), IL4 2 (127n), IL4+GDC 1 (131n), IL4+GDC 2 (128n), IL4+TRAM 1 (130c), IL4+TRAM 2 (129n), IFNgamma+LPS 1 (130n), IFNgamma+LPS 2 (127c), IFNgamma+LPS+TRAM 1 (126), IFNgamma+LPS+TRAM 2(129c), IFNgamma+LPS+GDC (128c)
(v) Quantitative phosphoproteomics to assess the effects of the B-Raf inhibitor GDC-0879 on IL-4-induced M2-type polarization and IFNgamma/LPS-induced M1-type polarization on THP-1-derived macrophages after 24 hours of treatment:
Phosphoproteome mapping on Orbitrap Fusion Lumos (one TMT set)
RAW files: Marneros_BRAF_inhibitor_phospho_fraction01 to ...fraction24, ...pY
7 samples
Labeling: IL4 1 (131c), IL4 2 (127n), IL4+GDC 1 (130n), IL4+GDC 2 (128n), IFNgamma+LPS 1 (128c), IFNgamma+LPS 2 (127c), IFNgamma+LPS+GDC (130c)
2019-12-10 | MSV000084672 | MassIVE