RNA seq analysis of primary human macrophages exposed to atheroma plaques homogenates with or without the Liver X receptor (LXR) antagonist GSK 2033
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE125126 | GEO | 2020/05/19
REPOSITORIES: GEO
Similar Datasets
Project description:RNA seq analysis of primary human macrophages exposed to atheroma plaques homogenates with or without the Liver X receptor (LXR) antagonist GSK 2033
| PRJNA515293 | ENA
Project description:To investigate how LXR activation potentiates expression of Th2 cytokine-dependent genes in primary human macrophages, we pulsed macrophages with synthetic LXR ligand T0901317 then polarized cells to alternatively activated macrophages with IL-4 or IL-13.
2021-04-14 | GSE158022 | GEO
Project description:Macrophages represent a major immune cell population in atherosclerotic plaques and play central role in the progression of this lipid-driven chronic inflammatory disease. Targeting immunometabolism is proposed as a strategy to revert aberrant macrophage activation to improve disease outcome. Here, we show ATP citrate lyase (Acly) to be activated in inflammatory macrophages and human atherosclerotic plaques. We demonstrate that myeloid Acly deficiency induces a stable plaque phenotype characterized by increased collagen deposition and fibrous cap thickness, along with a smaller necrotic core. In-depth functional, lipidomic, and transcriptional characterization indicate deregulated fatty acid and cholesterol biosynthesis and reduced liver X receptor (LXR) activation within the macrophages in vitro. This results in macrophages that are more prone to undergo apoptosis, whilst presenting increased phagocytosis of apoptotic cells. Together, our results indicate that targeting macrophage metabolism improves atherosclerosis outcome and we reveal Acly as a promising therapeutic target to stabilize atherosclerotic plaques.
2020-02-18 | GSE126690 | GEO
Project description:Atherosclerosis is an inflammatory disease linked to elevated blood cholesterol levels. Despite ongoing advances in the prevention and treatment of atherosclerosis 1, cardiovascular disease remains the leading cause of death worldwide 2. Continuous retention of apolipoprotein B-containing lipoproteins in the subendothelial space causes a local overabundance of free cholesterol. Since cholesterol accumulation and deposition of cholesterol crystals (CCs) triggers a complex inflammatory response 3 4, we tested the therapeutic potential of increasing cholesterol solubility in experimental atherogenesis. Here we show that treatment of murine atherosclerosis with the cyclic oligosaccharide 2-hydroxypropyl-β-cyclodextrin (CD), a compound that solubilizes lipophilic substances, reduced atherosclerotic plaque size, cholesterol crystal load and promoted plaque regression even under continuing Western diet. CD solubilized CCs and promoted cholesterylester and oxysterol production in macrophages leading to liver X receptor (LXR)-mediated transcriptional reprogramming. CD increased cholesterol efflux from macrophages and substantially augmented reverse cholesterol transport in vivo. Furthermore, CD reduced proinflammatory cytokines in vivo and decreased macrophage responsiveness towards TLR and inflammasome activation. Since CD treatment in humans is safe and CD beneficially affects key pathogenetic factors in atherogenesis it may thus be used clinically to prevent or treat human atherosclerosis .
2016-05-06 | GSE67013 | GEO
Project description:Atherosclerosis is an inflammatory disease linked to elevated blood cholesterol levels. Despite ongoing advances in the prevention and treatment of atherosclerosis 1, cardiovascular disease remains the leading cause of death worldwide 2. Continuous retention of apolipoprotein B-containing lipoproteins in the subendothelial space causes a local overabundance of free cholesterol. Since cholesterol accumulation and deposition of cholesterol crystals (CCs) triggers a complex inflammatory response 3 4, we tested the therapeutic potential of increasing cholesterol solubility in experimental atherogenesis. Here we show that treatment of murine atherosclerosis with the cyclic oligosaccharide 2-hydroxypropyl-β-cyclodextrin (CD), a compound that solubilizes lipophilic substances, reduced atherosclerotic plaque size, cholesterol crystal load and promoted plaque regression even under continuing Western diet. CD solubilized CCs and promoted cholesterylester and oxysterol production in macrophages leading to liver X receptor (LXR)-mediated transcriptional reprogramming. CD increased cholesterol efflux from macrophages and substantially augmented reverse cholesterol transport in vivo. Furthermore, CD reduced proinflammatory cytokines in vivo and decreased macrophage responsiveness towards TLR and inflammasome activation. Since CD treatment in humans is safe and CD beneficially affects key pathogenetic factors in atherogenesis it may thus be used clinically to prevent or treat human atherosclerosis .
2016-05-06 | GSE67011 | GEO
Project description:The objective of the study was to figure out the impact of LXR signaling on human macrophages. Primary human macrophages in an early differentiating and a mature differentiation state were treated with the LXR agonist T091317 for 4 and 24 h and transcriptome-wide expression analysis were performed. As LXRa is highly induced during macrophage differentiation and 68% of all LXRs targets change their expression during this process, we suggest that LXRs have essential functions in macrophage development. More than 238 genes are regulated in early as well as mature macrophages by activation of LXRs; most of them are up-regulated. LXRs administrate differentiation state specific as well as common macrophages functions related primarily to lipid homeostasis, immune response and cell fate. Interestingly, almost only genes related to lipid and cholesterol metabolism are overrepresented among early induced genes, whereas genes related to immune functions respond later, implying the existence of indirect mechanisms of control. Furthermore, in early differentiating macrophages cell proliferation and cell death associated genes are induced after 24 h of LXR activation, whereas in mature macrophages, showing high LXRa expression, the same functional cluster respond far earlier (4 h) after LXR ligand treatment. In conclusion, our data suggest that LXRs are modulators of macrophage differentiation, operating principally as positive transcriptional regulators of genes involved in lipid and cholesterol metabolism and by this indirectly influencing the immunophenotype of macrophages. CD14 positive cells of healthy donors were isolated by magnetic separation and differentiated in the presence of human serum to macrophages. At an early differentiating state (16 h after isolation) and at in mature differentiating state (day 11 after isolation) the cells were treated with the synthetical LXR agonist T091317 respective its solvent DMSO for 4 and 24 h. RNA was isolated and a whole genome microarray was performed.
2014-12-19 | E-GEOD-35967 | biostudies-arrayexpress
Project description:Bone marrow derived macrophages were isolated from C57BL/6J (LXR positive) and LXRalpha +LXRbeta double knockout mice (DKO) that had been treated with vehicle, Kado2-lipid A (KLA, and inflammatory stimulus), acetylated LDL (AcLDL, a mimic of pro-atherogenic lipoprotein particles) and GW3965 (GW, a synthetic LXR agonist) for 17 hours. Following treatment RNA was isolated and RNA-Seq was performed.
2018-08-17 | GSE118656 | GEO
Project description:The objective of the study was to figure out the impact of LXR signaling on human macrophages. Primary human macrophages in an early differentiating and a mature differentiation state were treated with the LXR agonist T091317 for 4 and 24 h and transcriptome-wide expression analysis were performed. As LXRa is highly induced during macrophage differentiation and 68% of all LXRs targets change their expression during this process, we suggest that LXRs have essential functions in macrophage development. More than 238 genes are regulated in early as well as mature macrophages by activation of LXRs; most of them are up-regulated. LXRs administrate differentiation state specific as well as common macrophages functions related primarily to lipid homeostasis, immune response and cell fate. Interestingly, almost only genes related to lipid and cholesterol metabolism are overrepresented among early induced genes, whereas genes related to immune functions respond later, implying the existence of indirect mechanisms of control. Furthermore, in early differentiating macrophages cell proliferation and cell death associated genes are induced after 24 h of LXR activation, whereas in mature macrophages, showing high LXRa expression, the same functional cluster respond far earlier (4 h) after LXR ligand treatment. In conclusion, our data suggest that LXRs are modulators of macrophage differentiation, operating principally as positive transcriptional regulators of genes involved in lipid and cholesterol metabolism and by this indirectly influencing the immunophenotype of macrophages.
2014-12-19 | GSE35967 | GEO
Project description:Mycobacterium tuberculosis (Mtb) is a life-threatening pathogen in humans. Bacterial infection of macrophages usually triggers strong innate immune mechanisms, including IL-1 cytokine secretion. The newer member of the IL-1 family, IL-36, was recently shown to be involved in cellular defense against Mtb. To unveil the underlying mechanism of IL-36 induced antibacterial activity, we analyzed its role in the regulation of cholesterol metabolism, together with the involvement of Liver X Receptor (LXR) in this process. Here we report that, in Mtb-infected macrophages, IL-36 signaling modulates cholesterol biosynthesis and efflux via LXR. Moreover, IL-36 induces the expression of cholesterol-converting enzymes and the accumulation of LXR ligands, such as oxysterols. Ultimately, both IL-36 and LXR signaling play a role in the regulation of antimicrobial peptides expression and in Mtb growth restriction. These data provide novel evidence for the importance of IL‑36 and cholesterol metabolism mediated by LXR in cellular host defense against Mtb.
2018-02-14 | GSE103092 | GEO
Project description:To identify novel LXR target genes, we conducted transcriptional profiling studies using RAW264.7 cells ectopically expressing LXRalpha Total RNA was isolated from RAW264.7 macrophages ectopically expressing LXRalpha as described in Venkateswaran et al. (2000); PNAS 97, 12097-12102. Cells were cultured with DMSO or GW3965 (1 μM) and LG268 (100 nM). Transcriptional profiling was performed at the UCLA microarray core facility using murine Affymetrix 430 2.0 microarrays.
2009-08-01 | E-GEOD-17088 | biostudies-arrayexpress