Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Dimethyl Itaconate alleviates the pyroptosis of macrophages through oxidative stress

ABSTRACT: Macrophages are involved in the pathophysiology of many diseases as critical cells of the innate immune system. Pyroptosis is a form of macrophage death that induces cytokinesis of phagocytic substances in the macrophages, thereby defending against infection. Dimethyl itaconate (DI) is an analog of itaconic acid with anti-inflammatory effects. However, the effect of dimethyl itaconate on macrophage pyroptosis has not been elucidated clearly. Thus, the present study aimed to analyze the effect of DI treatment on a macrophage pyroptosis model (Lipopolysaccharide, LPS+Adenosine Triphosphate, ATP). The results showed that 0.25 mM DI ameliorated macrophage pyroptosis and downregulated interleukin (IL)-1β expression. Then, real-time quantitative polymerase chain reaction (RT-qPCR) was used to confirm the result of RNA-sequencing of the upregulated oxidative stress-related genes (Gclc and Gss) and downregulated inflammation-related genes (IL-12β and IL-1β). In addition, Gene Ontology (GO) enrichment analysis showed that differential genes were associated with transcript levels and DNA replication. Kyoto encyclopedia of genes and genomes (KEGG) enrichment showed that signaling pathways, such as tumor necrosis factor (TNF), Jak, Toll-like receptor and IL-17, were altered after DI treatment. N-acetyl-L-cysteine (NAC) reversed the DI effect on the LPS+ATP-induced macrophage pyroptosis and upregulated the IL-1β expression. Oxidative stress-related protein Nrf2 is involved in the DI regulation of macrophage pyroptosis. Taken together, these findings suggested that DI alleviates the pyroptosis of macrophages through oxidative stress.

ORGANISM(S): Mus musculus

PROVIDER: GSE185895 | GEO | 2021/10/16

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Dimethyl itaconate inhibits secondary wave of NF-κB signaling in macrophage activation

Project description:Natural metabolite itaconate and its membrane permeable derivative dimethyl itaconate (DI) selectively inhibit a subset of cytokines during macrophage activation (e.g. IL-1β, IL-6, IL-12 but not TNF-α). Selectivity of DI action stems from the inhibitory effects of secondary, but not primary, wave of NF-κB signaling.

2018-04-21 | GSE110749 | 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

Dimethyl Itaconate alleviates the pyroptosis of macrophages through oxidative stress

Project description:Dimethyl Itaconate alleviates the pyroptosis of macrophages through oxidative stress

| PRJNA771138 | ENA

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-1β-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.

2016-07-01 | GSE82043 | GEO

Expression data from A549 cell line infected with influenza A virus (IAV) and treated with/without Itaconate

Project description:Analysis of gene expression in A549 cells infected with influenza A virus or Mock and treated with Itaconic acid (IA), or Dimethyl itaconate (DI) to investigate the effects itaconate have on transcriptional response in A549 cells. We particularly looked at anti-inflammatory effects of itaconate in inflammation followed by Influenza A virus infection.

2021-10-31 | GSE162260 | GEO

Expression data from hiPSC derived WT and ISG15 KO endothelial cells stimulated with interferon-a and treated with itaconic acid, dimethyl itaconate, 4-octyl itaconate and ruxolitinib

Project description:Analysis of gene expression in WT and ISG15 KO endothelial cells, stimulated with IFNa and treated with Itaconic acid (IA), Dimethyl itaconate (DI), 4-octyl itaconate (4OI) and ruxolitinib (RUX) to investigate the effects of treatments on transcriptional response in the cells.

2022-06-07 | GSE168747 | GEO

Expression data from differentiated THP-1 (dTHP-1) cell line infected with influenza A virus (IAV) and treated with/without Itaconate

Project description:Analysis of gene expression indTHP-1 cells infected with influenza A virus or Mock and treated with Itaconic acid (IA), or Dimethyl itaconate (DI) to investigate the effects itaconate have on transcriptional response in dTHP-1 cells. We particularly looked at anti-inflammatory effects of itaconate in inflammation followed by Influenza A virus infection.

2021-10-31 | GSE162261 | GEO

Electrophilic stress induced by dimethyl itaconate regulates IkB-zeta-mediated inflammatory responses

Project description:Interplay between metabolic state of the cell and its ability to undergo immunological activation has been recently recognized as a treasure chest of novel fundamental regulatory principles. Itaconate, and its membrane permeable derivative dimethyl itaconate (DI) were recently shown to selectively inhibit subset of cytokines during macrophage activation (e.g. Il1b, il6, Il12b but not TNF), yet the precise mechanism of this effect remained unclear. We find that selectivity of DI action stems from the inhibitory effects of electrophilic stress exerted by DI on IkB-zeta protein translation, leading to selective control of the secondary wave of Nfkb-signaling. Mechanistically, DI leads to glutathione depletion and subsequent activation of both Nrf2-dependent and Nrf2-independent stress responses. We find that IkB-zeta regulation is carried out in Nrf2-independent manner, and identify Atf3 as a key mediator of DI effects on IkB-zeta/IL6. This inhibitory effect is conserved across species and cell types, as evident from inhibition of IkB-zeta production in activating human monocytes and IL-17A stimulated keratinocytes of both human and mice. Finally, DI administration in vivo ameliorated IL17/IkB-zeta-driven skin pathology in the mouse model of psoriasis, highlighting therapeutic potential of this regulatory pathway.

2018-04-21 | GSE102190 | GEO

10x single-cell RNAseq profiling of influenza Virus infected Human PBMCs treated with Dimethyl itaconate

Project description:Itaconic acid and its variant Dimethyl itaconate (DI) have shown an anti-inflammatory effect in different human cell lines and PBMCs during Infleunza A virus (IAV) infection. In this experiment, we further explored which cell types in PBMCs respond to IAV infection and DI treatment.

2021-10-31 | GSE164922 | GEO

Electrophilic stress induced by itaconate and its derivatives regulates ATF3-IKBZ inflammatory axis independently of Nrf2 induction

Project description:Metabolic regulation recently emerged as a novel powerful principle guiding immune responses. The natural metabolite itaconate and its membrane permeable derivative dimethyl itaconate (DI) were recently shown to selectively inhibit a subset of cytokines during macrophage activation, yet the precise mechanism of this effect remained unclear. We show here that itaconate/DI react with glutathione and subsequently induce both Nrf2-dependent and Nrf2-independent stress responses. We find that the striking selectivity of DI action stems from the inhibitory effects of electrophilic stress on IKBZ protein translation, leading to the inhibition of only the secondary wave of NF-KB signaling. We find that IKBZ regulation occurs in an Nrf2-independent manner, and identify ATF3 as a key mediator of the immunosuppression.

2018-02-25 | MSV000082101 | MassIVE

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data