TRAIL expressing monocyte/macrophages reduce inflammation and attenuate atherosclerosis
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA420960 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Circulating TRAIL is reduced in cardiovascular disease patients and TRAIL deletion in mice exacerbates disease. The source of TRAIL and protective mechanism(s) are unclear. Monocyte TRAIL mRNA was reduced from coronary artery disease patients, strikingly associating with reduced plasma TRAIL. A strong inverse correlation between plasma TRAIL and IL-18 was observed, with IL-18 repressing monocyte TRAIL mRNA. In mice, two sources were investigated using bone-marrow (BM) transplants; TRAIL expressed only in BM (BM-TRAIL) or everywhere except BM (parenchymal-TRAIL), vs. whole-body TRAIL ablation (null-TRAIL). BM-TRAIL attenuated macrophage content and atherosclerosis. BM-derived macrophages with TRAIL deletion were more inflammatory, with impaired migration and reduced expression of cholesterol efflux, efferocytosis and nitric oxide-controlling genes. TRAIL expression also reduced islet macrophage content, but only parenchymal-TRAIL islets had improved function. Recombinant TRAIL administration stimulated insulin expression and islet mass. We propose TRAIL maintains monocyte/macrophage homeostasis and limits the progression of atherosclerosis and islet dysfunction.
2019-12-03 | GSE107645 | GEO
Project description:Background: Chronic inflammation is an important driver in the progression of non-alcoholic steatohepatitis (NASH) and atherosclerosis. The complement system, one of the first lines of defense in innate immunity, has been implicated in both diseases. However, the potential therapeutic value of complement inhibition in the ongoing disease remains unclear. Methods: After 20 weeks of high-fat diet (HFD) feeding, obese Ldlr-/-.Leiden mice were treated twice a week with an established anti-C5 antibody (BB5.1) or vehicle control. A separate group of mice was kept on a chow diet as a healthy reference. After 12 weeks of treatment, NASH was analyzed histopathologically, and genome-wide hepatic gene expression was analyzed by next-generation sequencing and pathway analysis. Atherosclerotic lesion area and severity were quantified histopathologically in the aortic roots. Results: Anti-C5 treatment considerably reduced complement system activity in plasma and MAC deposition in the liver but did not affect NASH. Anti-C5 did, however, reduce the development of atherosclerosis, limiting the total lesion size and severity independently of an effect on plasma cholesterol but with reductions in oxidized LDL (oxLDL) and macrophage migration inhibitory factor (MIF). Conclusion: We show, for the first time, that treatment with an anti-C5 antibody in advanced stages of NASH is not sufficient to reduce the disease, while therapeutic intervention against established atherosclerosis is beneficial to limit further progression.
2022-09-19 | GSE195614 | GEO
Project description:The project was designed to identify genes with an altered expression in macrophages from subjects with atherosclerosis compared to macrophages from control subjects. Experiment Overall Design: We used monocyte-derived macrophages from peripheral blood cultured in the absence or presence of oxidized LDL, baseline macrophages or foam cells. The macrophages were obtained from 15 subjects with subclinical atherosclerosis and a family history of CHD. Macrophages from 15 age and sexmatched subjects with no atherosclerosis and no family history of CHD were used as control.
2008-06-17 | E-GEOD-9874 | biostudies-arrayexpress
Project description:Resolving monocytes generated through TRAM deletion attenuate the pathogenesis of atherosclerosis
| PRJNA755439 | ENA
Project description:To further analyze the change of microRNA (miRNA) between TRAIL-sensitive and TRAIL-resistant Bel-7402 cells Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)
2015-10-20 | GSE74130 | GEO
Project description:The study aimed to investigate the impact of TRAIL on primary human M1, M2a and M2c macrophage polarization. Primary human monocyte-derived macrophages were pre-stimulated with TRAIL and then either left unpolarized (M0) or polarized into M1, M2a, or M2c phenotypes Then, RNA sequencing analysis was performed in 4 healthy donors including treated and control groups for one time point to analyze the differentially expressed M1 and M2 markers in TRAIL treated vs control groups.
2023-09-11 | GSE227737 | GEO
Project description:Atherosclerosis is a chronic inflammatory disease. Lesion progression is primarily mediated by cells of the monocyte/macrophage lineage. Interleukin-17A is a pro-inflammatory cytokine, which modulates immune cell trafficking and is involved inflammation in (auto)immune and infectious diseases. But the role of IL-17A still remains controversial. In the current study we investigated effects of IL-17A on advanced murine and human atherosclerosis, the common disease phenotype in clinical care. 26-weeks old apolipoprotein E-deficient (Apoe-/-) mice were fed a standard chow diet and treated either with IL-17A mAb (n=15) or irrelevant immunoglobulin (n=10) for 16 weeks. Furthermore, essential mechanisms of IL-17A in atherogenesis were studied in vitro. Inhibition of IL-17A markedly prevented atherosclerotic lesion progression (P=0.001) by reducing inflammatory burden and cellular infiltration (P=0.01) and improved lesion stability (P=0.01). In vitro experiments showed that IL-17A plays a role in chemoattractance, monocyte adhesion, sensitization of antigen-presenting cells toward pathogen-derived TLR4 ligands. Also, IL-17A induced a unique transcriptome pattern in monocyte-derived macrophages distinct from known macrophage types. Stimulation of human carotid plaque tissue ex vivo with IL-17A induced a pro-inflammatory milieu and up-regulation of molecules expressed by the IL-17A-induced macrophage subtype. We here show for the first time that functional blockade of IL-17A prevents atherosclerotic lesion progression and induces plaque stabilization in advanced lesions in Apoe-/- mice. The underlying mechanisms involve reduced inflammation and distinct effects of IL-17A on monocyte / macrophage lineage. In addition, translational experiments underline the relevance for the human system. Effects of IL-17A on human monocyte-derived macrophages were assessed (n=2 per group).
2014-10-01 | E-GEOD-60824 | biostudies-arrayexpress
Project description:We used microarrays to profile monocytes to identify gene expression differences correlating with disease status in carotid artery atherosclerosis. We identified 1302 genes differentially expressed between control and affected subjects after correcting for clinical covariates. Differential expression was likely caused by unidentified risk factors or systematic manifestations of atherosclerosis itself. Monocytes were extracted from subjects with and without carotid atherosclerosis. Microarray hybridization was used to determine if expression patterns distinguish the subjects.
2011-07-30 | E-GEOD-23746 | biostudies-arrayexpress
Project description:Investigation of the change of the Trail-dependent NK cell transcriptome during short-term (24h) infection with lymphocytic choriomeningitis virus (LCMV). RNA sequencing-based transcriptomics analysis was performed in spleen-isolated (NK1.1+CD3-) NK cells from 3 naïve Trail+/+ mice, 3 naive Trail-/- mice, 4 LCMV-infected Trail+/+ mice, and 4 LCMV-infected Trail-/- mice.
2019-08-27 | E-MTAB-7562 | biostudies-arrayexpress
Project description:T1 and G1 are the two melanoma cell lines, established from primary tumor (T1) and lymph node metastases (G1) of a 77 years old male patient. While G1 cells were resistant to TRAIL (TNF-related apoptosis-inducing ligand) mediated cell death, T1 cells exhibited a high dose- and time-dependent sensitivity to TRAIL. Cells were treated with or without of two doses (0.2 and 1ug/ml) of TRAIL for 24 h. Gene expression of each sample vs pool was measured. TRAIL-resistant metastatic G1 vs primary TRAIL-sensitive T1 was compared.
2006-01-01 | E-MEXP-247 | biostudies-arrayexpress