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Gene expression in macrophages in response to Acetylated-LDL (Ac-LDL)

ABSTRACT: Analysis of mouse thioglycollate-elicited peritoneal macrophages incubated in presence of acetylated low density lipoprotein (Ac-LDL) (120 μg/ml) for 24 h vs. mock-treated controls. Lipid accumulation in macrophages has profound effects on macrophage gene expression and contributes to the development of atherosclerosis. Angiopoietin-like protein 4 (ANGPTL4) is the most up-regulated gene in foamy macrophages and its absence in hematopoietic cells results in larger atherosclerotic plaques, characterized by bigger necrotic core areas and increased macrophage apoptosis.

ORGANISM(S): Mus musculus

PROVIDER: GSE83090 | GEO | 2016/06/21

SECONDARY ACCESSION(S): PRJNA324719

REPOSITORIES: GEO

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Single-cell RNA-sequencing of skin immune cells uncover a role for Angptl4-mediated ifi20b expression in monocyte cell fate differentiation during wound healing

Project description:Angiopoietin-like protein 4 (Angptl4) is a matricellular protein that associates with extracellular matrix proteins, mediating complex cell-cell, and cell-matrix interactions. It has been implicated in various inflammation-associated diseases, including wound healing, but very few reports describe a direct role for Angptl4 in the immune landscape of wound microenvironment. Here, we studied whether Angptl4 regulates the immune response during wound healing. Using single-cell RNA sequencing to examine the temporal changes in the immune cell landscape of excisional wounds from wild type and Angplt4-knockout (Angplt4-/-) mice revealed that Angptl4-/- wounds had a stalled inflammatory phase. Infiltrated neutrophils remained elevated in the Angptl4-/- wounds due to an impaired monocyte to macrophage differentiation needed for clearance. The impaired monocyte differentiation was also validated in wounds using multi-color flow cytometry. Pairwise comparisons of differentially expressed genes from wound-derived and bone-marrow derived macrophages demonstrated few differences, suggesting that Angptl4 has a confined regulome. We identified interferon activated protein 202B (ifi202b) to be consistently upregulated in Angptl4-/- macrophages. . Pathway analysis further confirmed that ifi202b significantly impacted multiple gene networks involved in the cell fate of monocytes and the functions of monocyte-derived macrophages. Taken altogether, we conclude that Angptl4 orchestrates the inflammatory state, innate immune landscape, and healing process in the wound microenvironment via its transcriptional regulation on ifi202b.

2022-03-02 | GSE186986 | GEO

PI3K signaling promotes formation of lipid-laden foamy macrophages at the spinal cord injury site

Project description:After spinal cord injury (SCI), infiltrating macrophages undergo excessive phagocytosis of myelin and cellular debris, forming lipid-laden foamy macrophages. To understand their role in the cellular pathology of SCI, investigation of foamy macrophage phenotype in vitro revealed a unique inflammatory profile, increased reactive oxygen species (ROS) production, and mitochondrialdysfunction. Bioinformatic analysis identified PI3K as a regulator of inflammation in foamy macrophages, and pharmacological inhibition of this pathway decreased lipid content and inflammatory cytokine and ROS production in these cells. Macrophage-specific inhibition of PI3K using liposomes significantly decreased foamy macrophages at the injury site after a mid-thoracic contusive SCI in mice. RNA sequencing and in vitro analysis of foamy macrophages revealed increased autophagy after PI3K inhibition as a potential mechanism for reduced cellular lipid accumulation. Together, our data suggest that formation of pro-inflammatory foamy macrophages after SCI is due to activation of PI3K signaling that leads to decreased autophagy.

2023-12-05 | GSE237511 | GEO

Bulk RNA-seq of aorta intima resident macrophage from B6, and adventitia macrophages from ApoE-/- mice

Project description:Macrophages in atherosclerotic aorta are major population in lesion and contributes to lesion formation by becoming foam cells. To investigate in determine diversity of arterial macrophage, we extracted aorta intima resident macrophages (CD11c+ MHC II+ CD64+ macrophages from C57BL/6 mice, as well as adventitia macrophages from atherosclerotic aorta (which complement our prior submissions of foamy and non-foamy intima macrophage). Our data identify unique gene expression signatures for these different macrophage populations in the aorta.

2020-07-23 | GSE154921 | GEO

MicroRNA expression in thioglycollate and alternatively activated

Project description:Macrophage activation must be tightly controlled to prevent overzealous responses that cause self-damage. MicroRNAs have been shown to promote classical macrophage activation by blocking concomitant anti-inflammatory signals and transcription factors, but can also place restraints on activation by preventing excessive TLR-signalling. In contrast, the microRNA profile associated with alternatively activated macrophages and their role in regulating wound-healing or anti-helminthic responses has not yet been described. Utilizing an in vivo model of alternative activation, in which adult Brugia malayi nematodes are surgically implanted in the peritoneal cavity of mice, we examined the profile of microRNA expression in these alternatively activated macrophages and compared this to alternatively activated IL-4 receptor knockout macrophages and thioglycollate elicited macrophages. Peritoneal macrophages from BALB/c wild type or IL-4 receptor knockout mice were elicited with thioglycollate or using nemtodes (peritoneal implant of Brugia malayi). The latter leads to a population of alternatively activated macrophages. Microarray analysis was used to examine the microRNA profile of WT alternatively activated macrophages (n = 4), IL-4 receptor knockout alternatively activated macrophages (n = 4), WT thioglycollate elicited macrophages (n = 3) and IL-4 receptor knockout thioglycollate elicited macrophages (n = 3).

2012-08-07 | E-GEOD-35047 | biostudies-arrayexpress

Genome-wide analysis of mouse macrophages stimulated with IL-4 (Biogel and thioglycollate macrophages) (Affymetrix)

Project description:Analysis of alternative activation of macrophages at gene expression level. The study forms part of a wider study where we compare the effects of IL-4 in different human and mouse macrophages. Our results support the notion that in vitro culture conditions greatly affect the macrophage response to IL-4. Total RNA obtained from Thioglycollate and Biogel elicited peritoneal macrophages exposed to 20 ng/ml of IL-4 for 18 hours. Biogel and thioglycollate elicited macrophages were stimulated with the Th2 cytokine IL-4, for RNA extraction and hybridization on Affymetrix microarrays.

2012-09-29 | E-GEOD-35436 | biostudies-arrayexpress

Genomic profile of foamy and non-foamy granuloma macrophages from fat-fed ApoE null mice or control mice fed a normal diet

Project description:Formation of foam cell macrophages (FCMs), which sequester extracellular modified lipids, is a key event in atherosclerosis. How lipid loading affects macrophage phenotype is controversial, with evidence suggesting either pro- or anti-inflammatory consequences. To investigate this further, we compared the transcriptomes of foamy and non-foamy macrophages (NFMs) that accumulate in the subcutaneous granulomas of fed-fat ApoE null mice and normal chow fed wild-type mice in vivo. Consistent with previous studies, LXR/RXR pathway genes were significantly over-represented among the genes up-regulated in foam cell macrophages. Unexpectedly, the hepatic fibrosis pathway, associated with platelet derived growth factor and transforming growth factor-? action, was also over-represented. Several collagen polypeptides and proteoglycan core proteins as well as connective tissue growth factor and fibrosis-related FOS and JUN transcription factors were up-regulated in foam cell macrophages. Increased expression of several of these genes was confirmed at the protein level in foam cell macrophages from subcutaneous granulomas and in atherosclerotic plaques. Moreover, phosphorylation and nuclear translocation of SMAD2, which is downstream of several transforming growth factor-? family members, was also detected in foam cell macrophages. We conclude that foam cell formation in vivo leads to a pro-fibrotic macrophage phenotype, which could contribute to plaque stability, especially in early lesions that have few vascular smooth muscle cells. Samples (n=4/group): Foam cell macrophages (FCM) isolated from inflammatory sponges placed in ApoE null mice fed a high-fat diet (n=4), non-foamy macrophages (NFM) isolated from inflammatory sponges placed in control mice fed a normal diet (n=4).

2015-07-23 | E-GEOD-70126 | biostudies-arrayexpress

Bulk RNA-seq of foamy and non-foamy intimal macrophages from ApoE -/- mouse

Project description:Macrophages in atherosclerotic aorta are major population in lesion and contributes to lesion formation by becoming foam cells. To investigate in vivo transcriptome profiles of those macrophages, we extracted foamy and non-foamy macrophages from atherosclerotic aorta using lipid probe-based flow cytometry sorting. Our data indicates that intima non-foamy and foamy macrophages show different mRNA expressions. Rather than non-foamy macrophages, foamy macrophages expressed more genes related to cholesterol metabolism, oxidative phosphorylation, lysosome and so on. The non-foamy macrophages expressed more genes related to immune response (Il-1b related pathways, TNF, TLR signaling pathways) than foamy macrophages.

2018-08-30 | GSE116239 | GEO

Genome-wide analysis of human macrophages stimulated with IL-4

Project description:This SuperSeries is composed of the following subset Series: GSE5099: Expression Data from Macrophage Maturation and Polarization Experiment GSE35433: Genome-wide analysis of human macrophages stimulated with IL-4 (20ng/ml) (Illumina) GSE35434: Genome-wide analysis of human macrophages stimulated with IL-4 (10ng/ml) (Illumina) GSE35435: Genome-wide analysis of mouse macrophages stimulated with IL-4 (bone marrow macrophages) (Affymetrix) GSE35436: Genome-wide analysis of mouse macrophages stimulated with IL-4 (Biogel and thioglycollate macrophages) (Affymetrix) Refer to individual Series

2012-09-29 | E-GEOD-35495 | biostudies-arrayexpress

Genome-wide analysis of mouse macrophages stimulated with IL-4 (Biogel and thioglycollate macrophages) (Affymetrix)

2012-09-29 | GSE35436 | GEO

Effects of acLDL loading on macrophage

Project description:acLDL loading of mouse peritoneal macrophage is an in vitro foam cell model. We have used microarray analysis and proteomics to characterize the effects of acLDL loading on the cells. Macrophages were harvested from the peritoneum of C57Bl/6J mice 5 days after injection of thioglycolate. Thioglycollate elicited macrophage were cultured for 2 days in DMEM + 10%FBS either in the presence or absence of 50 microgram/mL acLDL. 4 indepdendent biological replicates were used for each condition.

2010-12-31 | E-GEOD-19926 | biostudies-arrayexpress

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