The immunomodulatory effects of IL-4 on monocyte-derived macrophages
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Masayuki Asano
PROVIDER: E-GEOD-75829 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Shared Molecules
Only show the datasets with similarity scores above: 0.5
Threshold
0.5
Similar Datasets
Project description:To explore the effects of sRANKL on tumor-associated macrophages, we first sorted CD14+ monocytes from peripheral blood mononuclear cells of healthy donors using magnetic-activated cell sorting and then induced their differentiation into macrophages by culture with M-CSF for 5 days. We then stimulated these macrophages with IL-4 (20 ng/ml) together with or without 100 ng/ml of sRANKL for 6 hours and examined gene expression using a cDNA microarray. sRANKL stimulated gene expression on monocyte-derived macrophages was measured at 6 hours after exposure to doses of 100 ng/ml sRANKL.
2015-08-24 | E-GEOD-72292 | biostudies-arrayexpress
Project description:To explore the effects of periostin on tumor-associated macrophagess, we first sorted CD14+ monocytes from peripheral blood mononuclear cells of healthy donors using magnetic-activated cell sorting and then induced their differentiation into macrophages by culture with M-CSF for 5 days. In the absence of IL-4 stimulation, these macrophages expressed CD163 and Arg1 (a marker of M2 macrophage activation) but not CD206, suggesting that they were similar to macrophages in the early stage of mycosis fungoides (low frequency of CD206+ cells and low IL-4 expression). We then stimulated these macrophages with or without 100 ng/ml of periostin for 6 hours and examined gene expression using a cDNA microarray. Periostin stimulated gene expression on monocyte-derived macrophages was measured at 6 hours after exposure to doses of 100 ng/ml periostin.
2015-07-14 | E-GEOD-70821 | biostudies-arrayexpress
Project description:Macrophage activation is the main immunological process occurring during the development of several diseases, and the heterogeneity of macrophage activation or differentiation has been suggested to be involved in disease progression. In the present study, we attempted to identify molecules specifically expressed on human classically activated macrophages (M1) to investigate the significance of the M1-like phenotype in human diseases. Human monocyte-derived macrophages were differentiated into M1, M2a, M2b, and M2c phenotypes, and gene expression profiles were analyzed by cDNA microarray analysis and were used for bioinformatics examination. The gene expression profiles of murine macrophages were additionally evaluated. We identified guanylate-binding protein 5 (GBP5), which is associated with leucine-rich repeat protein 3-mediated inflammasome assembly in the M1 macrophages of both humans and mice. Notably, GBP5 protein expression was detected in cultured M1 macrophages by Western blot analysis. GBP5 is a useful candidate marker of the M1 phenotype. CD14+ monocytes from human PBMC were cultured with GM-CSF(10 ng mLâ1) or M-CSF (50 ng mLâ1) for seven days to differentiate into macrophages.To induce macrophage subtypes [M1, M1(-), M2a, M2b, and M2c], the macrophages were further stimulated for 24 h with LPS (10 ng mLâ1) + IFN-γ (50 ng mLâ1), IFN-γ (50 ng mLâ1), IL-4 (10 ng mLâ1), IL-1β (10 ng mLâ1), and IL-10 (10 ng mLâ1). Control macrophages (M0) were prepared by incubating for 24 h without additional factors.Two independent experiments were performed using different donors.
2016-08-10 | E-GEOD-85346 | biostudies-arrayexpress
Project description:To evaluate gene expression profiles in intestinal epithelial cells (IEC) after OSM stimulation, we have employed whole genome microarray expression profiling as a discovery platform to identify relevant genes which are potentially of interest to reveal the role of OSM in intestinal inflammation. The most strongly up-regulated genes were SERPINS, which belong to the family of serin peptidase inhibitors with antiprotease activities, most of them serine and cysteine proteases. SERPINB4, SERPINB3 and SERPINA3 were the genes with the strongest up-regulation, also verified in qPCR. OSM-induced SERPIN up-regulation may contribute to anti-apoptotic and proliferative effects of OSM in IEC. HCT116 cells were starved overnight with medium containing 1% FCS after reaching 70% confluency. On the next day, cells were stimulated in quadruplicates with 100 ng/mL OSM or left unstimulated. RNA was isolated 6 hours after stimulation and RNA concentration and purity was measured.
2014-12-13 | E-GEOD-53295 | biostudies-arrayexpress
Project description:Tumor-associated macrophages (TAMs) are known to be involved in progression, angiogenesis and motility of various cancers. We have previously reported the association between increased number of infiltrating TAMs with tumor progression and poor prognosis in esophageal squamous cell carcinomas (ESCCs). To study roles of TAMs in ESCC, we first exposed peripheral blood monocytes (PBMo) derived macrophages from healthy volunteers to conditioned media of TE series human ESCC cell line (TECM) and confirmed the induction of expression of M2 macrophage marker, CD204, and protumorigenic factors, interleukin (IL)-10, VEGFA and MMPs. Next, we compared gene expression profile between PBMo-derived macrophages and PBMo-derived macrophages stimulated with TECM by cDNA microarray. Based on the result, we focused on growth differentiation factor 15 (GDF15) among highly expressed genes including IL-6, IL-8 and CXCL1. Immunohistochemical study on 70 cases of surgically resected ESCCs revealed that GDF15 was detected not only in macrophages but also in cancer cells. High expression of GDF15 in ESCCs was significantly correlated with more malignant phenotypes including lymph and blood vessel invasion, lymph node metastasis as well as clinical stages. Patients with high expression of GDF15 showed poor disease-free survival (p = 0.011) and overall survival (p = 0.041). Furthermore, we found that recombinant human GDF15 promote cell proliferation and phosphorylation of both Akt and Erk1/2 in ESCC cell lines in vitro. These results indicate that GDF15 is secreted by both TAMs and cancer cells in tumor microenvironment and is associated with aberrant growth and poor prognosis of human ESCC. We exposed PBMo-derived macrophages from healthy volunteers to TECM and observed their acquisition of TAM-like characters in this study. We further investigated specific cancer-associated gene expression profile in TECM induced TAM-like macrophages by cDNA microarray analysis.
2014-08-01 | E-GEOD-59948 | biostudies-arrayexpress
Project description:In psoriasis lesions, a diverse mixture of cytokines is upregulated which influence each other generating a complex inflammatory situation. Although this is the case, the inhibition of Interleukin-17A (IL-17A) alone showed unprecedented clinical results in patients, indicating that IL-17A is a critical inducer of psoriasis pathogenesis. To elucidate IL-17A-driven keratinocyte-intrinsic signaling pathways, we treated monolayers of normal human epidermal keratinocytes in vitro with a mixture of 6 cytokines (IL-17A, TNF-a, IL-17C, IL-22, IL-36g and IFN-g) involved in psoriasis, to mimic the inflammatory milieu in psoriasis lesions. Microarray and gene set enrichment analysis revealed that this cytokine mixture induced similar gene expression changes with the previous transcriptome studies using psoriasis lesions. Importantly, we identified a set of IL-17A-regulated genes in keratinocytes, which recapitulate typical psoriasis genes exemplified by DEFB4A, S100A7, IL19 and CSF3, based on differences in the expression profiles of cells stimulated with 6 cytokines versus cells stimulated with only 5 cytokines lacking IL-17A. Furthermore a specific IL-17A-induced gene, NFKBIZ, which encodes IkappaB-zeta, a transcriptional regulator for NF-kappaB, was demonstrated to have a significant role for IL-17A-induced gene expression. Thus, we present novel in vitro data from normal human keratinocytes that would help elucidating the IL-17A-driven keratinocyte activation in psoriasis. Cytokine mixture-induced gene expression in primary normal human epidermal keratinocytes (NHEKs) was measured at 24 hours after exposure. NHEKs were exposed to the combination of selected six cytokines (IL-17A: 100 ng/ml, TNF-a: 10 ng/ml, IFN-g: 10 ng/ml, IL-17C: 100 ng/ml, IL-22: 100 ng/ml, IL-36g: 500 ng/ml) , or to the different combinations of five of the six cytokines (in total, 7 different treatments and one untreated control). No replicate experiments were conducted.
2016-03-08 | E-GEOD-77719 | biostudies-arrayexpress
Project description:Macrophages are known to be polarized into inflammatory (M1) and immunoregulatory (M2) cells when they are stimulated by agonists such as IFN-gamma and IL-4, respectively. If circulating monocytes may be polarized in response to T cell signals is often misguidedly deduced from macrophage results. Here the transcriptional responses of human CD14+ monocytes to IFN-gamma and IL-4 were analyzed using whole genome microarrays. A principal component analysis and hierarchical clustering showed that monocyte and macrophage responses were distinct. Monocytes stimulated with IFN-gamma and IL-4 for 6 hours exhibited some features of macrophage polarization. Indeed, when 80 genes considered as M1 and M2 genes were analyzed, we found that M1 genes were modulated in response to IFN-gamma and that M2 genes were modulated in response to IL-4. The M1 polarization of monocytes was transient because only M2 genes were modulated when monocytes were stimulated with IFN-gamma and IL-4 for 18 hours. However, the activation of monocytes by IFN-gamma and IL-4 could not be reduced to M1/M2 polarization status. Indeed, monocytes exhibited early specific signatures composed of 46 and 39 up-regulated genes in response to IFN-gamma and IL-4, respectively, and a late signature common to both molecules that consisted of 57 up-regulated genes. Taken together, these results demonstrated the extreme plasticity of human monocytes and suggested the existence of a core transcriptional termination program. Using early and late signatures might be pertinent to investigate monocyte activation in inflammatory or infectious diseases. Monocytes were stimulated with IFN-gamma (20ng/mL) or IL-4 (20ng/mL) for 6 and 18 hours or culture for 6 and 18 hours without agonist (Unstimulated samples). Monocytes-derived-macrophages (MDM) stimulated with IFN-gamma and IL-4 for 18 hours were used as controls. Each microarray is derived from a single biological sample.
2013-03-15 | E-GEOD-36537 | biostudies-arrayexpress
Project description:To confirm the changed gene expression profiles in GPR15 knock out (KO) macrophages, we applied a SurePrint G3 Mouse Gene Expression service from Takara Bio Inc (Kusatsu, Shiga, Japan) to analyze gene expression profiles in lipopolysaccharide (LPS)-stimulated GPR15KO macrophages, comparing with wild type (WT) macrophages. Most significantly up-regulated genes in GPR15KO macropahges included Il6, Il17a, Il23, Tnfsf8, Il1b, Ifna2 and Ccnd2. On the contrary, several inflammation-related genes, including Ccl17, Itgax, Nrp1 and Rasgrf2, were down-regulated in WT macrophages, compared to GPR15 KO macrophages. Abdominal macrophages from WT and GPR15 KO mice were stimulated with PBS or LPS (100 ng/ml) for 4 hrs. Total RNA were extracted using a TRIzol-chloroform based method.
2016-08-25 | E-GEOD-86020 | biostudies-arrayexpress
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:Bone marrow-derived macrophages were produced from mice lacking IL-10 alone (IL10-def) or mice lacking both IL-10 and the p50/p105 subunit of NF-kB (p50/IL10), and left unstimulated, stimulated with LPS (1 ng/ml) or stimulated with LPS and IL-10 (0.3 ng/ml).
2011-01-10 | GSE19941 | GEO