Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA273989 | ENA |
REPOSITORIES: ENA
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Project description:The global change of the miR expression profile during atherosclerosis is due to the infiltration of different types of leukocytes into the arterial vessel wall in addition to disease-specific regulation in vascular cells. Monocyte-derived macrophage accumulation in the subintimal region is critical in the formation of atherosclerotic plaques. It is currently unknown which miRs are involved in the atherogenic macrophage response. The comparison of the miR expression profile in LPS/Interferon-gamma activated mouse macrophages with the miR expression in the unstimulated mouse macrophages was performed to detect M1-type macrophage-enriched miRs. This screening combined with our miR profiling in atherosclerotic vessels may help to identify M1-type macrophage-enriched miRs in atherosclerotic vessels that may play a role in the macrophage function during atherogenesis. Bone marrow cells were harvested from femura of 6- to 8-week-old female C57BL/6 mice, re-suspended in DMEM-F12/10% FCS/10% L929-conditioned medium, and cultured for 7 days to differentiate into primary macrophages. F4/80 and CD11b expression was determined by flow cytometry to confirm the macrophage phenotype. Macrophages were stimulated with LPS (100ng/ml, 14 hours) and INF-g (10ng/ml, 6 hours), and the M1 polarization was verified by quantification of mannose receptor C type 1 (MRC1), arginase II (ArgII), inducible nitric oxide synthase (iNOS), and arginase I (ArgI) by qRT-PCR. Total RNA (M1-type and unstimulated (MФ) macrophages) was isolated using the mirVana microRNA Isolation Kit.
2012-12-26 | E-GEOD-33453 | biostudies-arrayexpress
Project description:The global change of the miR expression profile during atherosclerosis is due to the infiltration of different types of leukocytes into the arterail vessel wall in addition to disease-specific regulation in vascular cells. Monocyte-derived macrophage accumulation in the subintimal region is critical in the formation of atherosclerotic plaques. It is currently unknown which miRs are involved in the atherogenic macrophage response. The comparison of the miR expression profile in LPS/Interferon-gamma activated mouse macrophages with the miR expression in the normal aortic vessel wall was performed to detect macrophage-enriched miRs. This screening may help to identify macrophage-enriched miRs in atherosclerotic vessels that may play a role in the macrophage function during atherogenesis. Bone marrow cells were harvested from femura of 6-8 week old female C57BL/6 mice, re-suspended in DMEM-F12/10% FCS/10% L929-conditioned medium, and cultured for 7 days to differentiate into primary macrophages. F4/80 and CD11b expression was determined by flow cytometry to confirm the macrophage phenotype. Macrophages were stimulated with LPS (100ng/ml, 14 hours) and INF-g (10ng/ml, 6 hours) and the M1 polarization was verified by quantification of mannose receptor C type 1 (MRC1), arginase II (ArgII), inducible nitric oxide synthase (iNOS), and arginase I (ArgI) by qRT-PCR. Total RNA (M1-type macrophages and aorta tissue) was isolated using mirVana microRNA Isolation Kit.
2014-01-01 | E-GEOD-26556 | biostudies-arrayexpress
Project description:Macrophages are phagocytic cells in the innate immune system that infiltrate into resident tissues and subsequently polarize into at least two classical phenotypes: ‘pro-inflammatory’ M1 and ‘anti-inflammatory’ M2. Aberrant polarization can aggravate the pathophysiology of infectious diseases such as tuberculosis. Understanding the mechanisms that influence macrophage biology can lead to pharmacological control of polarization. We have developed a novel triomics approach utilizing liquid chromatography-tandem mass spectrometry (LC-MS/MS) to perform simultaneous analysis of metabolites, proteins, and histone modifications. Using human blood derived monocytes that were polarized in vitro towards M1- (IFN-γ) and M2- (IL-4) phenotypes, we found that elevated nitric oxide production in M1 macrophages, inhibits oxidative phosphorylation and upregulates glycolytic pathways. Due to the uncoupling of glycolysis and the citric acid cycle/oxidative phosphorylation, an accumulation of acetylated amino acids was measured. Stable isotope tracing of glucose revealed reduced histone acetylation of certain key markers such as H3K27Ac, and others. We propose that the reduction could be due to trapping of excess acetyl-coA into acetylated amino acids. Furthermore, nitric oxide seems to irreversibly bind B12, a necessary co-factor for methionine synthase, inhibiting endogenous methionine synthesis, which could alter the histone epigenetic methylation and therefore downstream gene and protein expression. Triomics also allowed us to identify novel arginine methylation and Nα-acetylation of aspartate, glutamate, and ornithine. We conclude that triomics approach demonstrates a dynamic interplay between cellular metabolism and epigenetics and this axis can ultimately influence macrophage phenotype and gene expression.
2022-10-13 | PXD030701 | Pride
Project description:Pulmonary fibrosis (PF) is a terminal lung disease characterized by fibroblast proliferation, accumulation of extracellular matrix accumulation, inflammatory damage, and tissue structure destruction. The pathogenesis of this disease, especiallyparticularly idiopathic pulmonary fibrosis (IPF), is still remains unknown. Macrophages play a significant rolemajor roles in organ fibrosis diseases, including pulmonary fibrosis. The phenotype and polarization of macrophages are closely associated with the process of pulmonary fibrosis. A new direction in drug research on for antipulmonary fibrosis is focuseds on developing drugs that maintain the stability of the pulmonary microenvironment. Here, tThrough bioinformatics analysis and experiments involving bleomycininduced pulmonary fibrosis in mice, we confirmed the importance of macrophage polarization in IPF. The analysis revealed that macrophage polarization in IPF involves a change in the phenotypice spectrum. Furthermore, the experiments demonstrated showed high expression of M2-type macrophage-related-associated biomarkers and inducible nitric oxide synthase, thus indicating an imbalance in M1/M2 polarization of pulmonary macrophages in mice with pulmonary fibrosis. Our investigation revealed that the ethyl acetate extract (HG2) obtained from the roots of Prismatomeris connataPrismatomeris connata Y. Z. Ruan exhibits therapeutic efficacy against bleomycin-induced pulmonary fibrosis. HG2 demonstrates the ability to modulates macrophage polarization, alterations in the TGF‐β/Smads pSmad pathway, and downstream protein expression in the context of pulmonary fibrosis. Drawing upon On the basis of our findings, we believe that HG2 exhibits has potential as a novel component of traditional Chinese medicine component for treating pulmonary fibrosis.
2024-01-07 | PXD048007 | Pride
Project description:Classical stimulation of macrophages (MLPS/IFNγ) elicits the expression of inducible nitric oxide synthase (iNOS), generating large amounts of nitric oxide (NO) and inhibiting respiration. Consequent upregulation of glycolysis and a disrupted tricarboxylic acid (TCA) cycle underpin this switch to a pro-inflammatory phenotype. Here we show that the NOS cofactor tetrahydrobiopterin (BH4) modulates key aspects of metabolic remodelling in activated bone-marrow-derived macrophages (BMDMs) via NO production. Using two complementary mouse models that each lack the capacity for inducible NO generation, through different mechanisms, we reveal that NO regulates macrophage respiratory function via changes in the abundance of critical N-module subunits in Complex I, by HIF1α-mediated glycolytic remodelling, and by modulating levels of the critical TCA cycle metabolites, and inflammatory mediators, citrate, succinate, and itaconate. Taken together, our findings reveal new critical roles for iNOS-derived NO that are required for metabolic remodelling and cytokine production in macrophage inflammatory responses.
2019-05-31 | PXD010628 | Pride
Project description:Toxoplasma gondii is an obligate intracellular protozoan with anti-tumor activity against a variety of cancers. However, the therapeutic effect of T. gondii on colorectal cancer is unclear, and using direct Toxoplasma infection in immunotherapy involves safety concerns. This study investigated the anti-tumor effect and mechanism of exosomes derived from dendritic cells (DC) infected with T. gondii (Me49-DC-Exo). We used the density gradient centrifugation to isolate exosomes from uninfected DCs (DC-Exo) and T. gondii Me49-infected DCs (Me49-DC-Exo). The isolated exosomes were identified by transmission electron microscopy, nanoparticle tracking analysis, and western blotting. Me49-DC-Exo significantly inhibited tumor growth and reduced the proportion of M2 macrophages in the blood of tumor-bearing mice. In vitro, Me49-DC-Exo suppressed macrophage (RAW264.7) polarization to M2 phenotype. miRNA sequencing revealed that multiple miRNAs in Me49-DC-Exo were differentially expressed compared with DC-Exo. miR-182-5p, miR-155-5p, miR-125b-2-3p, and miR-155-3p were up-regulated, while miR-9-5p was significantly down-regulated. Transfecting mimics or inhibitors of these differential miRNAs into RAW264.7 cells showed that miR-155-5p promoted M1 macrophage polarization while inhibiting M2 macrophage polarization. Bioinformatics prediction and dual-luciferase reporter assay confirmed the suppressor of cytokine signaling 1 (SOCS1) as a direct target of miR-155-5p. Silencing SOCS1 gene expression in RAW264.7 cells increased CD86 + CD206 - M1 macrophage proportion and inducible nitric oxide synthase and tumor necrosis factor-α mRNA levels. However, arginase1 and transglutaminase 2 expression levels decreased. These results suggest that the exosomes inhibit macrophage polarization to M2 phenotype and regulate SOCS1 expression by delivering functional miR-155-5p. These findings provide new ideas for colorectal cancer immunotherapy.
2022-02-24 | GSE197114 | GEO
Project description:M1 macrophages induce protective immunity against infection, but also contribute to metabolic and inflammatory diseases. Here we show that he E3 ubiquitin ligase, MDM2, promotes the glycolytic and inflammatory activities of M1 macrophage by increasing the production of IL-1β, MCP-1 and nitric oxide (NO). Mechanistically, MDM2 triggers the ubiquitination and degradation of E3 ligase, SPSB2, to stabilize iNOS and increases production of NO, which s-nitrosylates and activates HIF-1α for triggering the glycolytic and pro-inflammatory programs in M1 macrophages. Myeloid-specific haplo-deletion of MDM2 in mice not only blunts LPS-induced endotoxemia and NO production, but also alleviates obesity-induced adipose tissue-resident macrophage inflammation. By contrast, MDM2 haplodeletion induces higher mortality, tissue damage and bacterial burden, and also suppresses M1 macrophage response, in the cecal ligation and puncture-induced sepsis mouse model. Our findings thus identify MDM2 as an activator of glycolytic and inflammatory responses in M1 macrophages by connecting the iNOS-NO and HIF-1α pathways.
2024-09-16 | GSE276736 | GEO
Project description:Identification of targets of SNO-CoA- and SCoR-mediated denitrosylation in HEK293 cells expressing inducible nitric oxide synthase.
2018-12-11 | PXD011881 | Pride
Project description:Inducible nitric oxide synthase (iNOS) plays a crucial role in controlling growth of mycobacteria, presumed to be via nitric oxide (NO) mediated killing. However, NOS enzymes can also signal through NO-independent pathways, and production of NO by NOS requires the cofactor tetrahydrobiopterin (BH4). We compared Nos2-/- mice to mice with macrophage BH4 deficiency (Gch1fl/flTie2cre), due to a leukocyte-specific deletion of Gch1, to uncover the specific contribution of NO-independent NOS functions to anti-mycobacterial immunity. We used microarrays to detail the global programme of gene expression in uninfected and BCG infected macrophages that were either deficient in iNOS (Nos2-/- vs C57bl6/J) or BH4/Gch1 (GCHfl/flTie2cre vs GCHfl/fl)
2018-11-30 | GSE107543 | GEO
Project description:Macrophages are very plastic and play key roles in maintenance of tissue homeostasis. In cancer progression, macrophages also take parts through all the processes, from the initiation, progression, to the final tumor metastasis. Although energy deprivation and autophagy are widely used for cancer therapy, most of these strategies are not meant to target macrophages resulting in undesired effects and unsatisfactory outcomes for cancer immunotherapy. Herein, we developed a lanthanum nickel oxide (LNO) nanozyme that possesses phosphatase-like activity for ATP hydrolysis. Meanwhile, the autophagy of macrophages induced by LNO promotes the polarization of macrophages from M2-like macrophage (M2) to M1-like macrophage (M1) and reduces tumor-associated macrophages in tumor-bearing mice, exhibiting capability of killing tumor-associated macrophage and anti-tumor effect in vivo. Furthermore, pre-coating by myeloid cell membrane on the surface of LNO significantly enhanced antitumor immunity. Our findings demonstrate that phosphatase-like nanozyme, LNO can specifically induce macrophage autophagy that improves therapeutic efficacy and offers valuable strategies for cancer immunotherapy.
2024-08-10 | PXD051695 | Pride