Effect of IL-8 and VEGFA on polarization of tumor-associated macrophages
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE283259 | GEO | 2025/02/26
REPOSITORIES: GEO
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Project description:Effect of IL-8 and VEGFA on polarization of tumor-associated macrophages
| PRJNA1192969 | ENA
Project description:Fulminant myocarditis (FM) is a rapid, severe form of myocarditis requiring urgent mechanistic insight. While anti-interleukin-18 (IL-18) antibodies show promise in other inflammatory diseases, IL-18’s role in FM remains unknown. Here, we found that plasma IL-18 levels in FM patients negatively correlated with ejection fraction and positively with NT-proBNP. Elevated IL-18 was confirmed in a coxsackievirus B3 (CVB3)-induced murine FM model, with macrophages identified as the primary cellular source. Exogenous IL-18 promoted M1 macrophage polarization without affecting cardiomyocytes or fibroblasts. Neutralizing IL-18 antibodies (IL-18nAbs) suppressed M1 polarization and chemokine secretion in vitro, and improved survival, reduced myocardial M1 infiltration, and preserved cardiac function in vivo. Mechanistically, IL-18 activated the JAK1-STAT1 axis in macrophages; STAT1 silencing abrogated IL-18-driven M1 polarization. IL-18 also induced IFN-γ, and IFN-γ neutralization blocked Stat1 and Nos2 upregulation. Myeloid-specific IL-18R1 deletion alleviated CVB3-induced cardiac dysfunction and inflammation. Collectively, IL-18, primarily from macrophages, drives FM progression via JAK1-STAT1, representing a key pathogenic factor and therapeutic target.
2026-07-08 | GSE337837 | GEO
Project description:The proteasome is a central regulatory hub for intracellular signaling by degrading numerous signaling mediators. Immunoproteasomes are specialized types of proteasomes known to be involved in shaping adaptive immune responses, but their role for innate immune signaling is elusive. Here, we analyzed immunoproteasome function for polarization of alveolar macrophages which are highly specialized tissue macrophages of the alveolar surface of the lung. Classical activation (M1 polarization) of primary alveolar macrophages by LPS/IFNγ transcriptionally induced all three immunoproteasome subunits LMP2, LMP7, and MECL-1. In contrast, IL-4 triggered alternative (M2) activation was accompanied by posttranscriptional upregulation of LMP2 and LMP7. Accordingly, immunoproteasome activity increased in M1 cells, and to some extent under M2 conditions. Analyzing the polarization capability from LMP7 deficient mice revealed no effect on the LPS/IFNγ triggered M1 profile, but uncovered a distorted M2 profile for IL-4 stimulated LMP7-/- alveolar macrophages as characterized by increased M2 marker gene expression and CCL17 cytokine release. This shift in immunoproteasome-dependent M2 polarization was accompanied by amplified AKT/STAT6 activation and IRF4 expression in LMP7-/- alveolar macrophages. IL-13 stimulation of LMP7 deficient cells induced a similar M2 skewed profile and IL4Rα protein expression was generally elevated in LMP7-/- alveolar macrophages, indicating that amplified IL4R signaling in immunoproteasome defective cells may contribute to augmented M2 polarization. Importantly, treatment with an LMP7-specific proteasome inhibitor recapitulated the findings of genetic LMP7 inactivation. Our results thus suggest a novel role of immunoproteasome function for regulating innate immune function of macrophages by limiting IL4R expression and signaling. Expression data of M0 and M2 macrophages derived from Lmp7 k.o. and control animals
2016-06-29 | E-GEOD-72000 | biostudies-arrayexpress
Project description:Neovascularization is a major cause of blindness in various retinal diseases, and inflammation aggravates the pathological and clinical conditions of these diseases. VEGFA or ANG-2 neutralizing antibodies have been used to block pathological neovascularization. In this work, the effects of intraocular administration of neutralizing antibodies against VEGFA, ANG-2, or bispecific to these two factors on pathological findings were examined in the oxygen-induced retinopathy (OIR) mouse model. At both postnatal day (P)17 and P19, anti-VEGFA and -ANG-2 administration suppressed neovascularization, and the bispecific antibody attenuated neovascularization more efficiently. However, oxygen-induced vaso-obliteration was not modified by these antibodies. Numbers of photoreceptor, amacrine, and bipolar cells were reduced in the OIR retina, and the antibodies reversed these changes. Microglia-specific gene expression increased in the OIR retina, and administration of the antibodies reduced the IBA1-positive area in the OIR retina, although these antibodies did not affect marker gene expression. Labeled VEGFA and ANG-2 were found to be co-localized with microglia, suggesting that VEGFA and ANG-2 affect microglia activation directly. Taken together, neutralizing antibody to VEGFA or ANG-2 attenuated oxygen-induced neovascularization and inflammation, and the bispecific antibody more efficiently suppressed some features than the single antibody to VEGFA or ANG-2.
2026-04-15 | GSE315511 | GEO
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
Project description:Macrophage efferocytosis plays a central role in the regulation of inflammation and tissue homeostasis. Regulatory T (Treg) cells are known to influence macrophage function, but the impact of macrophage phagocytosis of apoptotic Treg cells on macrophage polarization remains poorly understood. In this study, bone marrow–derived macrophages (BMDMs) were co-cultured with apoptotic Treg cells or conventional CD4⁺ T (Tconv) cells. Apoptosis of T cells was induced by ATP/NAD⁺ treatment, and CD27 downregulation was used as an indicator of sensitivity to ATP/NAD⁺-mediated cell death. Treg and Tconv cells were labeled with anti-CD4 antibodies conjugated to BV421 or Alexa647 to enable detection of phagocytosis. BMDMs and apoptotic T cells were co-cultured under three conditions: non-polarizing conditions, IFN-γ stimulation, or IL-10 stimulation. After 48 hours of co-culture, macrophages were sorted based on phagocytosis status into three populations: macrophages that had phagocytosed Treg cells, macrophages that had phagocytosed Tconv cells, and macrophages that had not phagocytosed T cells. RNA sequencing was then performed to characterize transcriptional changes associated with phagocytosis of different T cell subsets and polarization conditions.
2026-05-15 | GSE325329 | GEO
Project description:Macrophage polarization and synovitis play significant roles in rheumatoid arthritis (RA). Chemokines are involved almost throughout the entire pathology of synovitis. However, the interaction between chemokines and macrophage polarization in RA has been seldom reported. This study found that chemokine C-C motif ligand 7 (CCL7) secreted by polarized M1 macrophages enhances M1 polarization, creating a positive feedback loop and revealing the role of CCL7 in the progression of rheumatoid arthritis. In this research, RNA sequencing indicated that M1 polarized macrophages secrete a large amount of CCL7, which further enhances M1 polarization. Through immunohistochemistry and enzyme-linked immunosorbent assay, it was found that the expression of CCL7 in the synovial tissue and serum of RA patients and mice was upregulated. Intra-articular injection of CCL7 recombinant protein exacerbated M1 polarization of macrophages, inflammation, fibrosis in the synovial tissue, and worsened arthritis pain in mice, which was improved after the injection of CCL7 neutralizing antibody. In addition, CCL7 promoted M1 polarization of macrophages and reversed the M2 polarization induced by IL-4, and it also promoted macrophage proliferation and migration. Although it had an inhibitory effect on chondrocyte activity, it did not show a significant impact on chondrocyte metabolism. Mechanistically, CCL7 targets CCR1 to promote M1 polarization of macrophages, a process partly mediated through the activation of the JAK2/STAT1 pathway. When stimulated by CCL7, macrophages secreted a vast amount of pro-inflammatory factors, exacerbating synovitis and cartilage damage, leading to the aggravation of RA disease. Our research established a positive feedback loop between M1 polarization of macrophages and CCL7, indicating that blocking CCL7 could improve the progression of RA, suggesting CCL7 as a potential target for RA treatment.
2025-01-08 | GSE267151 | GEO
Project description:Macrophage polarization and synovitis play significant roles in rheumatoid arthritis (RA). Chemokines are involved almost throughout the entire pathology of synovitis. However, the interaction between chemokines and macrophage polarization in RA has been seldom reported. This study found that chemokine C-C motif ligand 7 (CCL7) secreted by polarized M1 macrophages enhances M1 polarization, creating a positive feedback loop and revealing the role of CCL7 in the progression of rheumatoid arthritis. In this research, RNA sequencing indicated that M1 polarized macrophages secrete a large amount of CCL7, which further enhances M1 polarization. Through immunohistochemistry and enzyme-linked immunosorbent assay, it was found that the expression of CCL7 in the synovial tissue and serum of RA patients and mice was upregulated. Intra-articular injection of CCL7 recombinant protein exacerbated M1 polarization of macrophages, inflammation, fibrosis in the synovial tissue, and worsened arthritis pain in mice, which was improved after the injection of CCL7 neutralizing antibody. In addition, CCL7 promoted M1 polarization of macrophages and reversed the M2 polarization induced by IL-4, and it also promoted macrophage proliferation and migration. Although it had an inhibitory effect on chondrocyte activity, it did not show a significant impact on chondrocyte metabolism. Mechanistically, CCL7 targets CCR1 to promote M1 polarization of macrophages, a process partly mediated through the activation of the JAK2/STAT1 pathway. When stimulated by CCL7, macrophages secreted a vast amount of pro-inflammatory factors, exacerbating synovitis and cartilage damage, leading to the aggravation of RA disease. Our research established a positive feedback loop between M1 polarization of macrophages and CCL7, indicating that blocking CCL7 could improve the progression of RA, suggesting CCL7 as a potential target for RA treatment.
2025-01-08 | GSE285977 | GEO
Project description:Macrophage activation is required for the control of innate and adaptive immune responses. The classification in M1 and M2 macrophages based on a combination of small numbers of membrane and soluble markers is operational in murine and human macrophages. If this classification may be extended to circulating monocytes is not elucidated. To answer such question, human monocytes were stimulated for 6 and 18 hours with IFN-gamma and IL-4, two canonical agonists of M1/M2 polarization in macrophages, and gene expression programs were investigated with whole genome microarrays. The temporal analysis of these programs showed marked differences to both IFN-gamma and IL-4. In 6-h stimulated monocytes, gene categories related to inflammatory and immune responses were enriched, and these monocytes exhibited a M1 and M2 polarization in response to IFN-gamma and IL-4, respectively, as found in macrophages. In 18-h stimulated monocytes, the categories related to innate immunity and metabolic pathways were enriched in response to IFN-gamma and IL-4, whereas PPAR signaling pathway was specifically enriched in response to IL-4. In addition, the M1 and M2 polarization induced by IFN-gamma and IL-4, respectively, was replaced by an original transcriptional program that did not depend on IFN-gamma and IL-4. This program appeared as networks around chemokines, NF-kappaB/MAP kinase pathways and MHC class II molecules. These results clearly demonstrated that monocyte activation consisted of an early polarized stage likely involved in effector responses and a delayed stage that may regulate host responses. The establishment of databases on human circulating monocytes using high throughput methods may be critical for pathophysiological and clinical non-invasive studies. Peripheral blood mononuclear cells (PBMCs) were isolated from leukopacks from normal blood donor buffy coats (Etablissement Français du Sang, Marseille, France) by Ficoll density gradient
2012-12-07 | E-GEOD-27658 | biostudies-arrayexpress
Project description:T cells from spleen and lymphnode were isolated with EasySep Mouse CD8+ T Cell Isolation kit. Isolated CD8+ T cells were stimulated and cultured with plate-bound anti-CD3 and soluble anti CD28 antiboies in Tc1 or Tc9 cell polarizing conditios. After 3-day of polarization, cell were transferred into a new well and culture for another 2-day. on day 5 after seeding, Tc1 and Tc9 cells were collected and sequenced. We used microarrays to detail the global programme of gene expression of Tc1 and Tc9 cells at day 5 polarization.
2024-01-07 | GSE239842 | GEO