Metformin on human macrophages
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ABSTRACT:
PROVIDER: PRJNA642127 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Metformin on human macrophages Human blood derived macrophages were treated with 10micromolar Metformin (Sigma-Aldrich) for 4h
2020-06-27 | GSE153318 | GEO
Project description:Proteomics of human monocyte-derived macrophages treated with Interferon-gamma (10 ng/ml) with and without Metformin 1 mM
2025-11-26 | PXD063628 | Pride
Project description:In this study, we investigated the effects of metformin on the differentiation of bone marrow-derived macrophages (BMDMs) and their potential role in cancer immunity. BMDMs were generated from bone marrow cells extracted from C57BL/6N mice and differentiated in the presence or absence of metformin. Our transcriptomic analysis, performed using the Clariom S Mouse microarrays, revealed changes in gene expression profiles between metformin-treated and untreated macrophages.
2025-06-13 | E-MTAB-14199 | biostudies-arrayexpress
Project description:Metformin is a front-line drug in the treatment of type-2 diabetes mellitus (T2DM). In addition to its antigluconeogenic and insulin-sensitizing properties, it has emerged as a potent inhibitor of the inflammatory response of macrophages. Specifically, metformin has been shown to reduce transcript levels of Il1b, the gene encoding the pro-inflammatory cytokine interleukin (IL)-1b, during long-term exposure of macrophages to the bacterial cell-wall component lipopolysaccharide (LPS). However, the extent to which metformin affects the early transcriptional response to LPS has never been investigated. Here, we show that metformin affects transcript levels of a large yet selective subset of LPS-responsive genes after only two hours of LPS exposure, mostly counteracting the effect of LPS rather than enhancing it. The affected genes are implicated in a variety of biological functions, in particular cellular movement and trafficking. Intriguingly, metformin affects transcript levels of Il1b at this early time point as well, but through a molecular mechanism fundamentally different from the regulation observed after longer exposure. While down-regulation of Il1b by metformin during the late stages of the LPS response has been shown to rely on stabilization of hypoxia-inducible factor (HIF)-1α and production of IL-10, Il1b inhibition at the early stage requires AMP-activated protein kinase (AMPK) activation but is independent of HIF-1α and IL-10. These results reveal an unexpected complexity in the anti-inflammatory properties of metformin and demonstrate that Il1b is down-regulated by distinct mechanisms in the early and late stages of the LPS response.
2021-08-30 | GSE131348 | GEO
Project description:Glioblastoma (GBM) remains the most aggressive primary adult brain cancer attributed to its immunosuppressive nature. Radiation therapy (RT) and concurrent temozolomide chemotherapy are the standard treatments for GBM. Emerging evidence indicates that metformin has potential as an anti-tumor agent that can reshape the immune landscape across various malignancies. We thus postulate that metformin may enhance the anti-tumor effect of RT by modulating the immunosuppressive milieu in GBM. We first explored multiple in vitro conditions, with or without pre-induction, and mimicked a tumor microenvironment to demonstrate a highly context-dependent effect of metformin on the polarization of bone marrow-derived macrophages (BMDMs). We then investigated the antitumor activity and immune-modulatory effects of metformin in combination with RT in GBM-bearing mice. The in vitro experiment showed that metformin inhibited the immunosuppressive effects of IL-4/IL-13 but also the immunostimulatory effects of Lipopolysaccharide (LPS) on BMDMs, demonstrating bidirectional immunomodulatory properties that depend on the baseline inflammatory stimulus. In a tumor cell co-culture environment, metformin exhibited context-dependent immunoregulatory effects, predominantly promoting M1-associated activation. Notably, concurrent metformin treatment counteracted M2 polarization typically induced by the tumor microenvironment. In a high m-MCSF inducted M2-dominated condition, metformin preferentially shifted the highly polarized M2 phenotype toward an M1-like state in a time- and dose-dependent manner but with limited promotion of M1 subtype maturation. RNAseq results on BMDM treated with metformin showed increased homeostasis. Metformin showed dose-dependent immunomodulatory effects when combined with RT in vitro. In syngeneic GBM mouse models, concurrent metformin + RT significantly prolonged survival and reduced tumor burden by reprogramming tumor-associated macrophages (TAMs), elevating intratumoral CD8+ T-cell infiltration and the CD8+/Treg ratio, increasing circulating CD8+ T cells, reversing RT-induced expansion of monocytic myeloid-derived suppressor cells (mMDSCs), and expanding CD4+ and CD8+ effector memory populations in peripheral blood. Metformin demonstrates inhibitory effects on M2 phenotype of macrophages. However, it is not a simple M2 inhibitor; instead, it functions primarily as a neutralizer of highly polarized macrophage states by promoting transcriptomic homeostasis. This context-dependent activity enables metformin to relieve the profoundly immunosuppressive TME of GBM, potentiate the anti-tumor effects of RT, and enhance systemic immune memory.
2026-08-11 | GSE342855 | GEO
Project description:To test the effects of metformin on the human gut micorbiome, we fist collected human stool samples. We processed the samples in vitro culturing under anaerobic condition for 24 hours using the rapidAIM assay and either and cultured them with metformin, or DMSO as a control. We know that metformin can alter the human gut microbiome and were interested in better analyzing which functional proceses were altered.
2021-03-16 | PXD016427 | Pride
Project description:Metformin rejuvenates adult rat oligodendrocyte progenitor cells (OPCs) allowing more efficient differentiation into oligodendrocytes and improved remyelination of CNS axons and therefore is of interest as a possible therapeutic in demyelinating diseases such as multiple sclerosis (MS). We set out to test whether metformin had a similar effect in human stem cell derived-OPCs. We assessed the suitability of human monoculture, organoid and transplantation into immunodeficient mice (chimera model) culture systems in simulating in vivo adult human oligodendrocytes, finding most close resemblance in the chimera model. Metformin increased myelin proteins and/or sheaths in all models even when human cells had fetal signatures. In the chimera model, metformin led to a marked increase in mitochondrial area both in the human transplanted cells and in the mouse axons with associated increase in transcripts related to mitochondrial function and metabolism. Human oligodendrocytes from MS brain donors treated pre-mortem with metformin also expressed similar transcripts suggesting that metformin’s brain effect is not cell-specific, altering metabolism in both oligodendrocytes and axons leading to more myelin production, in part through mitochondrial changes. This bodes well for ongoing clinical trials testing metformin for neuroprotection.
2024-12-10 | GSE282369 | GEO
Project description:The biguanide metformin has been shown to not only reduce circulating glucose levels but also suppress in vitro and in vivo growth of prostate cancer. However, the mechanisms underlying the anti-tumor effects of metformin in advanced prostate cancers are not fully understood. The goal of the present study was to define the signaling pathways regulated by metformin in androgen-receptor (AR) positive, castration-resistant prostate cancers. Our group used RNA sequencing (RNA-seq) to examine genes regulated by metformin within the C4-2 human prostate cancer cell line. Western blot analysis and quantitative RT-PCR were used to confirm alterations in gene expression and further explore regulation of protein expression by metformin. Data from the RNA-seq analysis revealed that metformin alters the expression of genes products involved in metabolic pathways, the spliceosome, RNA transport, and protein processing within the endoplasmic reticulum. Gene products involved in ErbB, insulin, mTOR, TGF-, MAPK, and Wnt signaling pathways are also regulated by metformin. A subset of metformin-regulated gene products were genes known to be direct transcriptional targets of p53 or AR. Together, our results suggest metformin regulates multiple pathways linked to tumor growth and progression within advanced prostate cancer cells.
2022-02-10 | GSE196343 | GEO
Project description:As our results suggested that metformin acts to limit mitochondrial ROS and calcium-mediated activation of IL-6, we reasoned it would likely affect other processes in alveolar macrophages triggered by exposure to particulate matter (PM). Therefore, we treated mice with metformin in the drinking water for 24 hours before we instilled PM intratracheally. We then flow-sorted alveolar macrophages from whole lung homogenates 24 hours later for transcriptomic analysis (RNA-Seq).
2018-10-05 | GSE98731 | GEO
Project description:Phase 1, first-in-human, open label study of CAR macrophages in HER2 overexpressing solid tumors.
| 2360169 | ecrin-mdr-crc