Single-cell RNA sequencing analysis of the effect of 4-octyl itaconate administration on gene expression in immune cells isolated from traumatic brain injury mice brain
Ontology highlight
ABSTRACT: 4-octyl itaconate regulates immune response of brain immune cells following traumatic brain injury.
Project description:The 4-octyl itaconate O1_is a type of cell-permeable itaconate derivative. Studies have shown that with an anti-fibrotic effect in systemic sclerosis, the OI also affects osteoclast differentiation. The aim of this study was to explore the molecular mechanisms underlying the effects of OI on myoblast differentiation by RNA-seq analysis.
Project description:Single-cell RNA sequencing analysis of the effect of 4-octyl itaconate administration on gene expression in immune cells isolated from traumatic brain injury mice brain
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.
Project description:WT and ISG15 KO macrophages were stimulated with interferon-a and treated with itaconic acid and 4-octyl itaconate as they are known for anti-inflammatory effects. In this experiment, we further explored how itaconic acid and 4-octyl itaconate can play its role keeping ruxolitinib as a positive control in order to inhibit JAK/STAT pathway
Project description:Here, we report that macrophage-derived itaconate exerts a significant suppressive effect on dendritic cell (DC) function. To delve deeper into the impact of itaconate on DCs, we treated bone marrow-derived dendritic cells with 4-OI, a derivative of itaconate, and conducted RNA-seq analysis. Gene-set enrichment analysis (GSEA) of 4-OI-treated DCs showed a general downregulation of innate immunity and immune-response pathways.
Project description:<p>The Krebs cycle-derived metabolite itaconate, whose production is catalyzed by immune response gene 1 (IRG1), has excellent potential to link immunity and metabolism in activated macrophages through alkylation or competitive inhibition of target proteins. In support of this, our previous study demonstrated that the stimulator of interferon genes (STING) signaling platform functions as a hub in macrophage immunity and has a profound impact on the prognosis of sepsis. Interestingly, we found that itaconate, an endogenous immunomodulator, can significantly inhibit the activation of STING signaling. Moreover, 4-octyl itaconate (4-OI), which is a permeable itaconate derivative, could alkylate cysteine sites 65, 71, 88, and 147 of STING, thereby inhibiting its phosphorylation and downregulating the production of related inflammatory factors. Furthermore, itaconate and 4-OI inhibited the production of inflammatory factors in sepsis models. Our results have broadened the role of the IRG1-Itaconate axis in immunomodulation and highlighted itaconate and its derivatives as potential therapeutic agents in sepsis.</p>
Project description:Analysis of gene expression in human PBMCs infected with influenza A virus or Mock and treated with Itaconic acid, Dimethyl itaconate or 4-Octyl itaconate to investigate the effects itaconate have on transcriptional response in human PBMCs. We particularly looked at anti-inflammatory effects of itaconate in inflammation followed by Influenza A virus infection.
Project description:RNA-sequencing demonstrated Acod1 (Aconitate decarboxylase 1) as one of the top genes induced by air polution particulate matter (PM) in macrophages. We therefore sought to determine the effect of both exogenous itaconate (4-octyl itaconate) and endogenous itaconate on PM-induced inflammation in macrophages through RNA sequencing.