Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

ERMAP improves inflammatory bowel disease by regulating macrophage and T cell functions

ABSTRACT: Background & aims: Both macrophages and T cells play a critical role in inflammatory bowel disease (IBD) development. Since our previous studies have shown that a novel immune checkpoint molecule ERMAP affects macrophage polarization and negatively regulate T cell responses, we investigated the effects of ERMAP on IBD progression in mice. Methods: Using an dextran sodium sulfate (DSS)-induced IBD mice model, knockdown of ERMAP in RAW264.7 macrophages, ERMAP gene knockout mice, and Global gene expression analysis by RNA-seq, We investigate the effect of ERMAP on IBD by regulation of T cells and macrophages, NOD-like receptor (NLR) protein family pathway in macrophages. Results: We show here that administration of ERMAP protein significantly increases the proportion of anti-inflammatory M2-type macrophages and inhibits T cell activation and proliferation in IBD mice induced by DSS. Knockdown of ERMAP in RAW264.7 macrophages reduces M2-type macrophage polarization and increases T cell responses. Adoptive transfer of macrophages from ERMAP knockout mice exacerbates DSS-induced IBD. Global gene expression analysis by RNA-seq shows that ERMAP inhibits the NLR protein family pathway in macrophages. Conclusions: Our results suggest that ERMAP protein has the potential to be used in the treatment of IBD by regulating macrophage and T cell functions.

ORGANISM(S): Mus musculus

PROVIDER: GSE212010 | GEO | 2022/08/28

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

CaP-coated Zn-Mn-Li alloys regulate osseointegration via influencing macrophage polarization in the osteogenic environment

Project description:To investigate the mechanism by which Zn alloy scaffold regulates macrophage polarization towards M2, we established RAW264.7 cell lines We then performed gene expression profiling using data obtained from RNA-seq in macrophages stimulated by three different sets of materials.

2024-02-09 | GSE224524 | GEO

Alcohol promotes macrophage M2b polarization in colitis by modulating the TRPV1-MAPK/NF-kB pathways

Project description:Macrophages are key immune cells in inflammatory bowel disease (IBD) that can exhibit different phenotypes and promote inflammation. Alcohol consumption is associated with increased risk and severity of IBD. We performed in vitro and in vivo experiments with dextran sodium sulfate-induced mice colitis model, peritoneal macrophages and RAW264.7 cell line to investigate the effect and mechanism of alcohol on macrophages in colitis. Our study has found that alcohol exacerbates colitis in mice, increases the aggregation of colonic macrophages, and promotes the production of various inflammatory factors. Alcohol increases lipopolysaccharides (LPS)-induced calcium influx in macrophages, which is inhibited by the TRPV1 antagonist Capsazepine (CPZ). Alcohol and LPS together induce M2b polarization of macrophages and promote the phosphorylation and nuclear translocation of P38, ERK1/2 and NF-κB, and could be inhibited by CPZ and NOD2 inhibitor. Thus, alcohol can aggravate experimental colitis in mice and promote macrophage M2b polarization through the TRPV1-MAPK/NF-kB pathways.

2023-07-24 | GSE237785 | GEO

RNA sequence analysis between ECM1- sufficient and -deficient peritoneal macrophage

Project description:We report the differential gene expression between ECM1- sufficient and -deficient peritoneal macrophage. Inflammatory bowel disease (IBD) comprises chronic relapsing disorders of the gastrointestinal tract characterized pathologically by intestinal inflammation and epithelial injury. Here, we uncover a new function of extracellular matrix protein 1 (ECM1) in promoting the pathogenesis of human and mouse IBD. ECM1 was highly expressed in macrophages, particularly tissue-infiltrated macrophages under inflammatory conditions, and ECM1 expression was significantly induced during IBD progression. The macrophage-specific knockout of ECM1 resulted in increased arginase 1 (ARG1) expression and impaired polarization into the M1 macrophage phenotype following LPS treatment.RNA-sequencing data indicated an alternative metabolic process and a higher arginine metabolic level in ECM1-deficient macrophages compared with ECM1-sufficient macrophages. A mechanistic study showed that ECM1 can negatively regulate M1 macrophage polarization through the GM-CSF/STAT5 signalling pathway. Pathological changes in mice with dextran sodium sulphate-induced IBD were alleviated by the specific knockout of the ECM1 gene in macrophages. Taken together, our findings show that ECM1 has an important function in promoting M1 macrophage polarization, which is critical for controlling inflammation and tissue repair in the intestine.

2019-11-22 | GSE140766 | GEO

Anti-tumor Effect and Action Mechanism of Exosomes Derived from Toxoplasma gondii-Infected Dendritic Cells in Mice Colorectal Cancer

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

Novel transcriptome signatures and markers defining murine macrophages at the extremes of the canonical M1 and M2 polarization spectrum

Project description:Classically (M1) and alternatively activated (M2) macrophages play distinct roles in various physiological and disease processes. Understanding the gene transcription programs that contribute to macrophage polarization along the M1/M2 spectrum may lead to new tools to detect and therapeutically manipulate macrophage phenotype. Here, we define the M1 and M2 macrophage signature through mRNA microarray. The M1 macrophage signature was defined by 629 up-regulated and 732 down-regulated genes while the M2 macrophage signature was formed by 388 up-regulated and 425 down-regulated genes. While a subset of probes was common to both M1 and M2 cells, others were exclusive to each macrophage subset. The common M1/M2 pathways were characterized by changes in various transcriptional regulators and signaling partners, including increases in Kruppel-like Factor (Klf) 4, but decreases in Klf2. To identify M1 and M2 biomarkers that help discriminate these populations, we selected genes that were increased during M1 or M2 differentiation but decreased in the opposite population. Among top novel M1-distinct genes, we identified CD38, G-protein coupled receptor 18 (Gpr18) and Formyl peptide receptor 2 (Fpr2). Among top M2 genes, we found early growth response protein 2 (Egr2) and Myc. We validated these genes by Real-Time PCR and developed a CD38/Egr2-based flow cytometry assay that discriminates between M1 and M2 macrophages. Overall, this work defines the M1 and M2 signature and identifies several novel M1 and M2 genes that may be used to distinguish and manipulate M1 and M2 macrophages. Total RNA was prepared from bone marrow-derived macrophages of wild-type mice (n=2-3 independent mice) treated in M0, M1 or M2 conditions (n=2-3 replicates per condition originating from different mice)

2015-12-08 | E-GEOD-69607 | biostudies-arrayexpress

Unraveling the mechanism of ethyl acetate extract from Prismatomeris connata Y. Z. Ruan root in treating pulmonary fibrosis: insights from bioinformatics, network pharmacology, and experimental validation

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

Expression data from macrophage maturation and polarization c-Myc in alternative macrophage activation experiments

Project description:In response to microenvironmental signals macrophages undergo different activation, indicated as classic/M1 and alternative/M2 polarization. C-Myc transcription factor could be an essential player in M2 polarization. Functional relevance of c-Myc in M2 macrophage biology is investigated by evaluating the effect of 100-58F4, on the transcriptional profile induced on human macrophages by IL-4. Human monocytes were obtained from normal donor buffy coats by two-step gradient centrifugation using Ficoll (Biochrom) and Percoll (Amersham). Non-adherent cells were discarded, and the purified monocytes were incubated for 7 days in RPMI 1640 (Biochom) supplemented with 10% FCS (HyClone) and 100 ng/mL M-CSF to obtain resting macrophages. Macrophage polarization was obtained by removing the culture medium and culturing cells in RPMI 1640 supplemented with 10% FCS and 100 ng/mL LPS plus 20 ng/mL IFN-gamma (M1 polarization) or 20 ng/mL IL-4 (M2 polarization) for 24 h. When needed, chemical inhibitors were added with IL-4.

2011-09-15 | E-GEOD-32164 | biostudies-arrayexpress

Macrophagic S100A4 drives macrophage protumor activation and promotes tumor growth through controlling PPAR-γ induction

Project description:The lipid-metabolism up-regulation-mediated M2 polarization provides tumor-associated macrophages (TAMs) with protumor phenotypes during tumor development and progression. However, how TAMs reprogram their lipid-metabolism responding to M2 activators remains unclear. Here, we report that S100A4 is a determinant of macrophage M2 polarization. We find that the growth of carcinoma grafts was impaired in myeloid S100A4-deficient mice. Coincidentally, ablating S100A4 in macrophages reduced their capability of macrophage into utilization utilize of exogenous fatty acids as their major energy source for oxidation. Mechanistic analysis demonstrates that the induction of PPAR-γ responding to Th2 cytokine, IL-4, was halted in s100a4-deleted TAMs, as well as in bone marrow-derived macrophages, and as well as in Raw264.7 cells. Further molecular analyses reveal that CD36, downstream from S100A4-PPARγ, is the major effector for lipid uptake of S100A4+ macrophages. FurthermoreImportantly, higher levels of S100A4 is closely associated with tumor resistance to chemotherapy in murine models as well as poor prognosis of cancer patients in clinic . Our study thus suggests that blocking S100A4 constitutes a treatment strategy to reprogram macrophages toward an antitumor state by inhibiting PPAR-γ-induction mediated gene up-regulation.

2021-06-30 | GSE161060 | GEO

Identification of pharmacologic inhibitors and activators of IL-4-induced macrophage polarization [THP-1 RNA-seq]

Project description:Macrophages polarize towards different subpopulations with distinct and partly antagonistic functions in various diseases. IFNγ/LPS-polarized M1-type macrophages can have antiangiogenic activity, whereas IL-4-induced M2-type macrophages can be proangiogenic and profibrotic. Therapeutic strategies to inhibit M2-type polarization while promoting M1-type polarization could serve to inhibit pathological angiogenesis and fibrosis. Here, by combining global quantitative time-course proteomics and phosphoproteomics with a small-molecule inhibitor screen we identify signaling events that promote specifically IL-4-induced and not IFNγ/LPS-induced macrophage polarization and found that the MEK inhibitor trametinib and the HDAC inhibitor panobinostat potently prevent M2-type macrophage polarization without inhibiting M1-type polarization. In contrast, selective B-Raf inhibition promotes M2-type polarization. Trametinib and panobinostat also blocked M2-type macrophage polarization and concomitantly angiogenesis and fibrosis in models of wound healing and neovascular age-related macular degeneration in vivo. Thus, these pharmacologic inhibitors could be utilized therapeutically to selectively block IL4-induced macrophage polarization and reduce pathologic angiogenesis and fibrosis.

2021-10-16 | GSE154346 | GEO

Identification of pharmacologic inhibitors and activators of IL-4-induced macrophage polarization [PBMC RNA-seq]

2021-10-16 | GSE154345 | GEO