Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA362954 | ENA |
REPOSITORIES: ENA
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Project description:Mesenchymal stromal cells (MSCs) sense and modulate inflammation and represent potential clinical treatment for immune disorders. However, many details of the bidirectional interaction between MSCs and the innate immune comaprtment are still unsolved. Here we describe an unconventional but functional interaction between pro-inflammatory classically activated macrophages (M1MФ) and MSCs, with CD54 playing a central role. CD54 was upregulated and enriched specifically at the contact area between M1MФ and MSCs. Moreover, the specific interaction induced calcium signaling and increased the immunosuppressive capacities of MSCs dependent on CD54 mediation. Our data demonstrate that MSCs can detect an inflammatory microenvironment via a direct and physical interaction with innate immune cells. This finding opens new perspectives for MSC-based cell therapy.
2017-01-24 | GSE93970 | GEO
Project description:Human intestinal macrophages contribute to tissue homeostasis in noninflamed mucosa through profound down-regulation of pro-inflammatory cytokine release. Here, we show that this down-regulation extends to Toll-like receptor (TLR)-induced cytokine release, as intestinal macrophages expressed TLR3-TLR9 but did not release cytokines in response to TLR-specific ligands. Likely contributing to this unique functional profile, intestinal macrophages expressed markedly down-regulated adapter proteins MyD88 and Toll interleukin receptor 1 domain-containing adapter-inducing interferon beta, which together mediate all TLR MyD88-dependent and -independent NF-kappaB signaling, did not phosphorylate NF-kappaB p65 or Smad-induced IkappaBalpha, and did not translocate NF-kappaB into the nucleus. Importantly, transforming growth factor-beta released from intestinal extracellular matrix (stroma) induced identical down-regulation in the NF-kappaB signaling and function of blood monocytes, the exclusive source of intestinal macrophages. Our findings implicate stromal transforming growth factor-beta-induced dysregulation of NF-kappaB proteins and Smad signaling in the differentiation of pro-inflammatory blood monocytes into noninflammatory intestinal macrophages. Comparison of unstimulated monocytes and macrophages, and flagellin stimulated monocytes and macrophages.
2010-07-07 | E-GEOD-22373 | biostudies-arrayexpress
Project description:Tumor microenvironment (TME) is an active player in malignant growth and spread. Changes in the composition and structure of TME and extracellular matrix can result in either suppression or facilitation of malignant tumor growth. Carcinoma‐associated fibroblasts, bone marrow-derived multipotent mesenchymal stromal cells (BMMSCs), tumor associated macrophages and other inflammatory cells all affect the composition of TME, proliferation and survival of cancer cells, angiogenesis, invasion and metastasis. The objective of this work was to investigate the effect of the interaction between bone marrow-derived BMMSCs and human oral tongue squamous cell carcinoma (OTSCC) cells in the processes of invasion and gene expression. Co-cultures of OTSCC cancer cells and BMMSCs in 3D organotypic invasion assay were used in addition to cell culture, immunological, microarray, and RNA interference techniques. Total number of 4 samples were analyzed. 2 replicates of cultured human oral tongue squamous cell carcinoma (OTSCC) cells, and 2 replicates of OTSCC cells co-cultured with bone marrow-derived multipotent mesenchymal stromal cells
2013-12-01 | E-GEOD-44458 | biostudies-arrayexpress
Project description:Periodontitis is a chronic inflammatory condition marked by an imbalance between proinflammatory and proresolution mediators, which affects the tissues supporting the teeth. Maresin1 (MaR1) is a specialized pro-resolving lipid mediator (SPM) produced by macrophages, known for its role in regulating inflammatory processes. This study aimed to investigate the effects of MaR1 at varying concentrations on human gingival mesenchymal stem cells (hGMSCs) within inflammatory environments.
2024-11-20 | PXD058076 |
Project description:We isolated non-hematopoietic cells from fibrotic and non-fibrotic human bone marrow and perfomed scRNAseq on them. We identified 3 different stromal populations and 2 populations of hematopoietic progenitors. Our analysis revealed mesenchymal stromal cells (MSC) as pro-fibrotic cells. MSCs were functionally reprogrammed with loss of their progenitor status and acquisition of a pro-fibrotic phenotype in the fibrotic bone marrow. Additionally, stromal cells exhibited an upregulation of pro-inflammatory mediators like S100A8/A9.
2020-11-03 | GSE156640 | GEO
Project description:In recent years, it has been recognized the central role of cell bioenergetics in regulating immune cell function and fate giving rise to the interest in immunometabolism, an area of research focused on the interaction between metabolic regulation and immune function. Immunometabolism has been studied in the modulation of macrophage polarization. Thus, early metabolic changes associated with the polarisation of macrophages into pro-inflammatory or pro-resolving cells under different stimuli have been characterized. Tumour-associated macrophages are among the most abundant cells in the tumour microenvironment; however, it exists an unmet need to study the effect of chemotherapeutics on macrophage immunometabolism. Here, a systems biology approach that integrates transcriptomics and metabolomics unveils the immunometabolic effects of trabectedin (TRB) and lurbinectedin (LUR), two intercalating DNA agents with proved antitumor activity in the low nanomolar range. Our results show that TRB and LUR activate human macrophages towards a pro-inflammatory functional phenotype by inducing a specific metabolic rewiring program that includes ROS production and changes in the mitochondrial inner membrane potential, increased pentose phosphate pathway, TCA cycle serine and methylglyoxal pathways in human macrophages. glutamine, aspartate, histidine, and proline consumption are increased whereas 50 nM TRB increases lactate release and oxygen consumption is depressed . The observed immunometabolic rewiring could explain additional antitumor activities of these compounds and open new avenues to design therapeutic interventions that specifically target the immunometabolic landscape in the treatment of cancer.
2023-06-25 | GSE235390 | GEO
Project description:Epoxygenases belong to the cytochrome P450 family and they generate epoxyeicosatrienoic acids (EETs) known to have anti-inflammatory effects but little is known about their role in macrophage function. By high-throughput sequencing of RNA (RNA-seq) in primary macrophages derived fromrodents and humans, we establish the relative expression of epoxygenases in these cells. Zinc-finger nuclease-mediated targeted gene deletion of the major rat macrophage epoxygenase Cyp2j4 (orthologue of human CYP2J2),resulted inreduced EET synthesis. Cyp2j4-/-macrophages have relatively increased PPARγ levels and show a pro-fibrotic transcriptome,displayingover-expression of a specific subset of genes (260 transcripts) primarily involved in extracellular matrix, with fibronectin being the most abundantly expressed transcript.Fibronectin expression is under the control of epoxygenase activity in human and rat primary macrophages. In keeping with the invitro findings, Cyp2j4-/- rats show up-regulation of type I collagen following unilateral ureter obstruction (UUO) of the kidney and quantitative proteomics analysis (LC-MS/MS) showed increased renal type I collagen and fibronectin protein abundance resulting from experimentally induced crescentic glomerulonephritis in these rats. Taken together, these results identify the rat epoxygenase Cyp2j4 as a determinant of a pro-fibrotic macrophage transcriptome that could have implications in various inflammatory conditions depending on macrophage function. Gene expression profile generated for macrophages in wild type and Cyp2j4 KO WKY rats
2015-02-10 | E-GEOD-65715 | biostudies-arrayexpress
Project description:Chronic low-grade visceral white adipose tissue (WAT) inflammation is a hallmark of metabolic syndrome in obesity. Here, we demonstrate that a specific subpopulation of adipose tissue perivascular (PDGFRb+) stromal cells, termed “fibro-inflammatory progenitors” (FIPs), activate pro-inflammatory signaling cascades shortly after the onset of high-fat diet feeding of mice and control the accumulation of pro-inflammatory macrophages in WAT. The activation of FIPs is mediated by the downregulation of ZFP423, identified here as a transcriptional co-regulator of NFkB. Biochemical analysis of ZFP423-protein complexes and ChIP-seq analysis reveal that ZFP423 suppresses the DNA-binding capacity of the p65 subunit of NFkB by inducing a co-regulator switch. Doxycycline-inducible expression of Zfp423 in PDGFRb+ cells suppresses inflammatory signaling in FIPs and attenuates macrophage accumulation within visceral WAT of obese mice. Conversely, inducible inactivation of Zfp423 in PDGFRb+ cells increases FIP activity, exacerbates adipose macrophage accrual, and promotes WAT dysfunction in obese mice. These studies implicate mural cells as sentinels and gatekeepers of adipose tissue inflammation in obesity.
2020-09-01 | GSE134868 | GEO
Project description:The purpose of this experiment was to determine changes in gene expression by bone marrow-derived macrophages (BMDMs) treated with synthetic human vs. rodent islet amyloid polypeptide (IAPP). Synthetic human IAPP at 15 uM aggregates to form fibrils in vitro, whereas rodent IAPP is non-amyloidogenic. We hypothesized that interaction of macrophages with human IAPP aggregates can activate pro-inflammatory signalling pathways in macrophages, as described for other amyloidogenic peptides.
2010-08-11 | GSE23534 | GEO
Project description:Macrophages acquire a pro-inflammatory M1 phenotype in response to microbial products or pro-inflammatory cytokines through incompletely understood molecular mechanisms. We recently described the induction of APOBEC3A-mediated cellular site-specific cytosine-to-uracil (C>U) RNA editing during M1 macrophage polarization. However, the functional significance of this RNA editing is unknown. Here, we find that cellular RNA editing by APOBEC3A can also be induced by influenza or Maraba virus infections in normal macrophages, and by interferons in tumor-associated macrophages. Gene knockdown and RNA Seq analyses show that APOBEC3A induces C>U RNA editing (range 7%-88%) of 209 exonic or UTR sites in 203 genes during M1 polarization of monocyte-derived macrophages. The highest level of deleterious protein-recoding C>U RNA editing is observed in THOC5, which encodes a key nuclear protein implicated in the export of mRNAs during M-CSF driven macrophage differentiation. Knockdown of APOBEC3A in M1 macrophages reduces pro-inflammatory IL6, IL23A, and IL12B gene expression, CD80 and CD86 surface protein expression, and TNF-α, IL-1β and IL-6 cytokine secretion, and increases glycolysis and glycolytic capacity. These results demonstrate that APOBEC3A cytidine deaminase plays an important role in transcriptomic and functional polarization of pro-inflammatory M1 macrophages.
2020-03-13 | GSE146867 | GEO