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IRG1 Inflammasome Proteomics Experiments

ABSTRACT: BMDMs of indicated phenotypes were stimulated with LPS for 24h and analyzed or restimulated with LPS for additional 3h and analyzed. In some experiments 1mM itaconate was added at 4h of LPS first stimulation.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Macrophage

SUBMITTER: Kate Lizotte

LAB HEAD: Sebastian Hayes

PROVIDER: PXD020089 | Pride | 2021-09-09

REPOSITORIES: Pride

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Dataset's files

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			Action	DRS
	Experiment_1_TMT1.mgf	Mgf
	Experiment_1_TMT1.pdResult	Other
	Experiment_1_TMT2.mgf	Mgf
	Experiment_1_TMT2.pdResult	Other
	Experiment_2_TMT1.mgf	Mgf

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Publications

Itaconate confers tolerance to late NLRP3 inflammasome activation.

Bambouskova Monika M Potuckova Lucie L Paulenda Tomas T Kerndl Martina M Mogilenko Denis A DA Lizotte Kate K Swain Amanda A Hayes Sebastian S Sheldon Ryan D RD Kim Hyeryun H Kapadnis Unnati U Ellis Abigail E AE Isaguirre Christine C Burdess Samantha S Laha Anwesha A Amarasinghe Gaya K GK Chubukov Victor V Roddy Thomas P TP Diamond Michael S MS Jones Russell G RG Simons Donald M DM Artyomov Maxim N MN

Cell reports 20210301 10

Itaconate is a unique regulatory metabolite that is induced upon Toll-like receptor (TLR) stimulation in myeloid cells. Here, we demonstrate major inflammatory tolerance and cell death phenotypes associated with itaconate production in activated macrophages. We show that endogenous itaconate is a key regulator of the signal 2 of NLR family pyrin domain containing 3 (NLRP3) inflammasome activation after long lipopolysaccharide (LPS) priming, which establishes tolerance to late NLRP3 inflammasome ...[more]

PMID: 33691097

Similar Datasets

Itaconate confers tolerance to late NLRP3 inflammasome activation

Project description:Gene expression in LPS-stimulated, LPS-tolerized or non-tolerized WT and Irg1-deficient BMDMs

2021-04-20 | GSE164383 | GEO

Comparative evaluation of metabolic, electrophilic, and immunologic effects of itaconate and its ester derivatives on macrophage activation

Project description:Itaconate is a metabolite naturally produced in large amounts in macrophages after exposure to immune stimulation. Following the discovery of itaconate’s immunoregulatory properties, several ester derivatives of this dicarboxylic acid were designed to further examine its role. We evaluated the metabolic, electrophilic, and immunologic profiles of macrophages treated with unmodified itaconate and a panel of itaconate derivatives. We found that only unmodified itaconate strongly enhances LPS-induced IFNb secretion after 12h pre-treatment. Thus, we compared the transcriptional profile of wild type and Irg1-/- cells, which are unable to produce itaconate, after 24h LPS stimulation. We find that cells lacking itaconate have impaired downstream type I interferon signaling, and that addition of itaconate Irg1-/- BMDMs restores this signaling back to levels comparable to wild type. This data highlights the role of itaconate as an immunoregulatory metabolite, and highlights the importance of using unmodified itaconate or genetic knockout models in future mechanistic studies.

2020-05-15 | GSE145950 | GEO

Itaconate links inhibition of succinate dehydrogenase with macrophage metabolic remodeling and regulation of inflammation

Project description:Remodeling of the tricarboxylic acid (TCA) cycle is a metabolic adaptation mechanism accompanying inflammatory macrophage activation. During this process, endogenous metabolites can adopt regulatory roles that govern specific aspects of inflammatory response, as recently shown for succinate, which regulates the downstream pro-inflammatory IL-1Î²-HIF1a axis. Itaconate is one of the most highly induced metabolites in activated macrophages, yet its functional significance remains unknown. Here, we show that itaconate modulates macrophage metabolism and effector functions via its effect on succinate dehydrogenase, by inhibiting conversion of succinate to fumarate. Through this action, itaconate exerts anti-inflammatory effects when administered in vitro and in vivo during macrophage activation and ischemia-reperfusion injury. Using newly generated Irg1-/- mice, which lack the ability to produce itaconate, we show that endogenous itaconate regulates succinate levels and function, changes in mitochondrial respiration, and inflammatory cytokine production during macrophage activation. These studies highlight itaconate as a major physiological regulator of the global metabolic rewiring and effector functions of inflammatory macrophages. Experiment 1: mature WT BMDM were treated for 12h with 0.25 mM dimethyl itaconate (DI) or vehicle (Unst) and then stimulated with LPS (E. coli 0111:B4; 100 ng/ml, 4h) (DI+LPS; LPS); Experiment 2: mature Irg1-/- BMDM were stimulated with LPS (E. coli 0111:B4; 100 ng/ml) and murine recombinant IFNg (50 ng/ml) for 24h.

2016-07-01 | E-GEOD-82043 | biostudies-arrayexpress

Effects of Irg1-itaconate or Hemin on gene expression in macrophages [RNA-seq]

Project description:To investigate the role of Irg1-itaconate or Hemin in macrophages, bone marrow-derived macrophages (BMDMs) from WT mice and Irg1 KO mice were extracted and cultured. After 7 days of cells culture, the BMDMs from WT mice were treated 120 μM 4-octyl itaconate (4-OI) for 15 h, 15 μM Hemin for 12 h, and the BMDMs from Irg1 KO mice and WT mice were treated Vehicle for 12 h. We then performed gene expression profiling analysis using data obtained from RNA-seq of 4-OI, Hemin or vehicle treated WT BMDMs and Irg1 KO BMDMs.

2024-06-28 | GSE221734 | GEO

Gene expression from bone-marrow derived macrophages.

Project description:Gene expression from WT and NFAT5 KO primary macrophage cultures. Keywords: Bone-marrow derived macrophages. We analyzed 4 arrays from each condition: unstimulated WT BMDMs, LPS stimulated WT BMDMs, unstimulated KO BMDMs, LPS stimulated KO BMDMs.

2012-01-20 | E-GEOD-26343 | biostudies-arrayexpress

Validation of itaconate modification on model proteins

Project description:This dataset was generated to confirm that +130 and +146 Da adducts observed in LPS-stimulated macrophages were produced by the itaconate metabolite. To this end, model proteins (bovine serum albumin and human KEAP1) were reacted in vitro with itaconate, and the correspondent adducts were analyzed by LC-MSMS

2021-07-22 | PXD019858 | Pride

Induction of type I interferons in macrophages requires MEF2A and is targeted by prostaglandin E2

Project description:BMDMs were generated via differentiation of bone marrow cells in culture media containing m-CSF for 7 day. Upon differentiation, BMDMs were left untreated or stimulated with LPS, IFNa, PGE2, LPS+PGE2, or IFNa+PGE2.

2021-06-01 | E-MTAB-9253 | biostudies-arrayexpress

ChIPseq to profile CDK9 and Hes1 occupancy in bone marrow-derived macrophages from C57BL/6 mice

Project description:We characterized the CDK9 and Hes1 occupancy on gene loci in conditions of unstimuated and LPS stimualtion in BMDMs BMDMs were left untreated or stimulated with LPS for 1 hour. CDK9 or Hes1 ChIP was performed and the DNA products were subject to ChIPseq

2016-06-13 | E-GEOD-77334 | biostudies-arrayexpress

Gene expression of Bone marrow-derived macrophages isolated in ERR-alpha knock-out mice

Project description:We investigated the molecular mechanisms by which ERRM-NM-1 negatively regulates TLR-signaling pathways. To examine this, we performed global gene expression analysis of ERRM-NM-1+/+ and ERRM-NM-1-/- BMDMs after LPS stimulation. Microarray analysis revealed that several genes encoding various TLR-negative regulators were downregulated in LPS-stimulated ERRM-NM-1-/- BMDMs, when compared with ERRM-NM-1+/+ BMDMs Bone marrow-derived macrophages were isolated in 6~8 week old male C57BL6 mice and then divided into 4 groups 1) Solvent control-treated ERRM-NM-1+/+ BMDM 2) LPS-treated ERRM-NM-1+/+ BMDM 3) Solvent control-treated ERRM-NM-1-/- BMDM 4) LPS-treated ERRM-NM-1-/- BMDM

2014-06-17 | E-GEOD-58515 | biostudies-arrayexpress

GR and BRG1 cistromes of murine primary bone marrow derived macrophages treated with LPS and Dex+LPS [ChIP-seq]

Project description:We mapped the genome wide binding profile of the chromatin remodeller BRG1 in wild type bone marrow derived macrophages (BMDMs) after 3h LPS and LPS plus Dex treatment by ChIPseq. Additionally, we profiled the GR cistrome in Dex + LPS-treated BMDMs after 3h treatment by ChIPseq.

2023-06-23 | GSE186512 | GEO

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