Gene expression profiling after stimulation of THP-1 cells with a2NTD
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE25490 | GEO | 2010/11/20
SECONDARY ACCESSION(S): PRJNA134701
REPOSITORIES: GEO
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Project description:Background: Identifying the immune components that are regulated by a2NTD, a peptide cleaved from the N-terminus of the a2 vacuolar ATPase. Methods: In this study, we used pathway-focused PCR arrays to determine the genes that are regulated in human monocytic cell line, THP-1 after a2NTD stimulation over time. Results: a2NTD up-regulated several cytokines including IL-1 alpha, IL-1 beta, and IL-10. Several chemokines were also upregulated including the MCP and MIP families. Conclusion: We believe a2NTD to be an immune modulator made by tumor cells that aid in preventing immune surveillance by up-regulating proteins in monocytes that are both pro-and anti-inflammatory in nature. The Human Inflammatory Response and Autoimmunity RTM-BM-2 ProfilerM-bM-^DM-" PCR Array profiles the expression of 84 key genes involved in autoimmune and inflammatory immune responses. It represents the expression of inflammatory cytokines and chemokines as well as their receptors. It also contains genes related to the metabolism of cytokines and involved in cytokine-cytokine receptor interactions. Thoroughly researched panels of genes involved in the acute-phase response, inflammatory response, and humoral immune responses are represented as well. Using real-time PCR, you can easily and reliably analyze expression of a focused panel of genes related to inflammatory and autoimmune responses with this array.
2010-11-20 | E-GEOD-25490 | biostudies-arrayexpress
Project description:The objective of the study was to discover new functions of chemokine CXCL9/MIG, a cationic chemokine that has antimicrobial properties. Human monocytic cell line, THP-1 cells were stimulated 4 hours with chemokine MIG or CCL2/MCP-1 (a chemokine that is not positively charged and has no antimicrobial activity). By using a 21,000 oligo-based DNA human microarray we analyzed gene expression profiles induced by MIG and by MCP-1. The gene expression profile induced by MIG was >85% different from that induced by MCP-1. MIG increased transcription of genes encoding various chemokines (including CCL3/MIP-1alpha, CCL4/MIP-1beta, CCL2/MCP-1 and CXCL8/IL-8), cytokines (TNF-alpha), indicating that MIG has an immunomodulatory effect on THP-1 cells. Additionally, MIG strongly up-regulated a set of genes identified as having tumor suppressor functions, including BTG2, BTG1, P21, IGFBP3, DSCR1 and genes encoding markers for mature leukocyte differentiation (PLAU, LPL, PLAUR etc). In parallel, MIG down-regulated the expression of oncogenes (MYC), and genes related to cell proliferation and cell cycle progression. This gene profile strongly suggested that the chemokine MIG had anti-proliferative activity and might induce THP-1 cells to undergo terminal differentiation.
2010-07-01 | E-FPMI-5 | biostudies-arrayexpress
Project description:5,6-Dimethylxanthenone-4-acetic acid (DMXAA), a tumor vascular disrupting agent, is shown here to have substantial activity as a single agent against human A375 melanoma xenografts in nude mice (94 % hemorrhagic necrosis after 24 h, and 26 days growth delay following single dose at 25 mg/kg). CD45+ cells in tumor tissue increased 5-fold over the first 3 days after treatment, which was due largely to an influx of CD11b+ Ly6G+ neutrophils. Using murine and human multiplex cytokine assays to dissect the cytokines produced by host stromal cells or by the melanoma cells, it was shown that both the stromal cells and the A375 melanoma cells produced cytokines capable of attracting neutrophils into the tumor. The same xenografts were also analyzed using human and mouse Affymetrix microarrays to separately identify tumor cell-specific (human) and stromal cell-specific (mouse) gene expression changes. DMXAA induced numerous stromal cytokine mRNAs, including IP-10, IL-6, MIP-1α/β, MIP-2, KC, RANTES, MIG, MCP-1 and IL-1β, many of which were also elevated at the protein level. Numerous human cytokine mRNAs were also induced including MCP-1, IL-8, GRO, VEGF, GM-CSF and IL-6, which again was in line with our protein data. Pathway analysis indicated that significant numbers of the stromal mRNAs induced by DMXAA are regulated downstream of TNF-α, interferon-β and NFκB. Our results suggest that DMXAA may have utility in combination therapy for human melanoma through the activation of pro-inflammatory signalling pathways and cytokine expression from both stromal and tumor cells, leading to haemorrhagic necrosis, neutrophil influx and growth inhibition. Microarrays were used to identify separately the abundance of tumour cell and stromal cell RNA in A375 melanoma xenografts, with and without treatment by the stromal targetting drug DMXAA.
2012-03-15 | E-GEOD-26308 | biostudies-arrayexpress
Project description:5,6-Dimethylxanthenone-4-acetic acid (DMXAA), a tumor vascular disrupting agent, is shown here to have substantial activity as a single agent against human A375 melanoma xenografts in nude mice (94 % hemorrhagic necrosis after 24 h, and 26 days growth delay following single dose at 25 mg/kg). CD45+ cells in tumor tissue increased 5-fold over the first 3 days after treatment, which was due largely to an influx of CD11b+ Ly6G+ neutrophils. Using murine and human multiplex cytokine assays to dissect the cytokines produced by host stromal cells or by the melanoma cells, it was shown that both the stromal cells and the A375 melanoma cells produced cytokines capable of attracting neutrophils into the tumor. The same xenografts were also analyzed using human and mouse Affymetrix microarrays to separately identify tumor cell-specific (human) and stromal cell-specific (mouse) gene expression changes. DMXAA induced numerous stromal cytokine mRNAs, including IP-10, IL-6, MIP-1α/β, MIP-2, KC, RANTES, MIG, MCP-1 and IL-1β, many of which were also elevated at the protein level. Numerous human cytokine mRNAs were also induced including MCP-1, IL-8, GRO, VEGF, GM-CSF and IL-6, which again was in line with our protein data. Pathway analysis indicated that significant numbers of the stromal mRNAs induced by DMXAA are regulated downstream of TNF-α, interferon-β and NFκB. Our results suggest that DMXAA may have utility in combination therapy for human melanoma through the activation of pro-inflammatory signalling pathways and cytokine expression from both stromal and tumor cells, leading to haemorrhagic necrosis, neutrophil influx and growth inhibition.
2012-03-15 | GSE26308 | GEO
Project description:Extracellular ATP and PGE2 are two cAMP-elevating agents inducing semi-maturation of human monocyte-derived dendritic cells (MoDCs). We have extensively compared the gene expression profiles induced by ATPγS and PGE2 in human MoDCs using microarray technology. At 6 h of stimulation, ATPγS initiated an impressive expression profile compared to that of PGE2 (1125 genes compared to 133 genes respectively) but after 24 h, the number of genes regulated by ATPγS or PGE2 was more comparable. Many target genes involved in inflammation have been identified and validated by quantitative RT-PCR experiments. We have then focused on novel ATPγS and PGE2 target genes in MoDCs including colony-stimulating factor-1 (CSF-1), MCP-4/CCL13 chemokine, vascular endothelial growth factor (VEGF-A) and neuropilin-1 (NRP-1). ATPγS strongly down-regulated CSF-1 receptor mRNA and CSF-1 secretion which are involved in monocyte and DC differentiation. Additionally, ATPγS down-regulated several chemokines involved in monocyte and DC migration including CCL2/MCP-1, CCL3/MIP-1alpha, CCL4/MIP-1beta, CCL8/MCP-2 and CCL13/MCP-4. Interestingly, VEGF-A – a major angiogenic factor displaying immunosuppressive properties - was secreted by MoDCs in response to ATPγS, ATP or PGE2, alone or in synergy with LPS. Finally flow cytometry experiments have demonstrated that ATPγS, ATP and PGE2 down-regulate NRP-1, a receptor playing inter alia an important role in the activation of T lymphocytes by DCs. Our data give an extensive overview of the genes regulated by ATPγS and PGE2 in MoDCs and an important insight into the therapeutic potential of ATP- and PGE2-treated human DCs. Keywords: Time course, treatment comparison
2008-03-01 | GSE8539 | GEO
Project description:After myocardial infarction (MI) activation of the immune system and inflammatory mechanisms, among others, can lead to ventricular remodeling and heart failure (HF). Interaction between these systemic alterations and corresponding changes in the heart has not been extensively examined in the setting of chronic ischemia. The main purpose of this study was to investigate alterations in cardiac gene and systemic cytokine profile in mice with post-ischemic HF. Plasma was tested for IgM and IgG anti-heart reactive repertoire and inflammatory cytokines. Heart samples were assayed for gene expression. Ischemic HF significantly increased the levels of serum IgM (by 5.2 fold) and IgG (by 3.6 fold) associated with remarkable content of anti-heart specificity. Comparable increase was observed in levels of circulating pro-inflammatory cytokines, such as IL-1β (3.8x) and TNF-α (6.0x). IFN-gamma was also increased in the MI group by 3.1x. However, IL-4 and IL-10 showed no significant difference between MI and sham groups. Chemokines such as MCP-1 and IL-8 were enhanced in the plasma of infarcted mice. We identified 2079 well annotated unigenes that were significantly regulated by the post-ischemic HF. Complement activation and immune response was among the most up-regulated processes. Interestingly, 21 out of the 101 quantified unigenes involved in inflammatory response were significantly up-regulated and none were down-regulated. These data indicate that post-ischemic heart remodeling is accompanied by immune mediated mechanisms that act both systemically and locally.
2009-10-24 | GSE18703 | GEO
Project description:After myocardial infarction (MI) activation of the immune system and inflammatory mechanisms, among others, can lead to ventricular remodeling and heart failure (HF). Interaction between these systemic alterations and corresponding changes in the heart has not been extensively examined in the setting of chronic ischemia. The main purpose of this study was to investigate alterations in cardiac gene and systemic cytokine profile in mice with post-ischemic HF. Plasma was tested for IgM and IgG anti-heart reactive repertoire and inflammatory cytokines. Heart samples were assayed for gene expression. Ischemic HF significantly increased the levels of serum IgM (by 5.2 fold) and IgG (by 3.6 fold) associated with remarkable content of anti-heart specificity. Comparable increase was observed in levels of circulating pro-inflammatory cytokines, such as IL-1β (3.8x) and TNF-α (6.0x). IFN-gamma was also increased in the MI group by 3.1x. However, IL-4 and IL-10 showed no significant difference between MI and sham groups. Chemokines such as MCP-1 and IL-8 were enhanced in the plasma of infarcted mice. We identified 2079 well annotated unigenes that were significantly regulated by the post-ischemic HF. Complement activation and immune response was among the most up-regulated processes. Interestingly, 21 out of the 101 quantified unigenes involved in inflammatory response were significantly up-regulated and none were down-regulated. These data indicate that post-ischemic heart remodeling is accompanied by immune mediated mechanisms that act both systemically and locally. We compared RNA samples extracted from whole hearts of control and infarcted mice samples by analyzing hybridization to AECOM 32k mouse microarrays (http://microarray1k.aecom.yu.edu/) spotted with Operon version 3.0 70-mer oligonucleotides. The hybridization protocol, the slide type and the scanner settings were uniform throughout the entire experiment to minimize the technical noise. Control (sham) and infarcted red-labeled heart samples were hybridized against an in-house prepared green-labeled universal mouse reference.
2010-06-20 | E-GEOD-18703 | biostudies-arrayexpress
Project description:Replacement therapy with coagulation factor VIII (FVIII) products concurrent with bleeds (on-demand) in hemophilia A (HA) patients, seems to increase the risk for developing anti-drug antibodies (i.e. inhibitors). A danger signal environment characterized by tissue damage and inflammation at the site of a bleed is thought to contribute to the anti-FVIII response. The nature of this inflammatory reaction is however not fully known. The purpose of this study was to characterize the inflammatory response, locally and systemically, during the first 24h following a knee joint bleed in the HA rat. HA rats received either a needle induced knee joint bleed (n=83) or a sham procedure (n=41). Blood samples were collected at selected time-points from 0-24h post injury/sham. Synovial fluid as well as intra-articular knee tissue and popliteal lymph nodes were collected at 24h. Cytokine and chemokine concentrations and mRNA gene expression on tissue samples were measured. Gene expression analysis revealed a rapid inflammatory response in the injured knees, accompanied by significantly increased levels of specific gene products in the synovial fluid; IL-1β, TNFα, KC/GRO, IL-6, Eotaxin, MCP-1, MCP-3, MIP-1α, MIP-2, RANTES, A2M and AGP. Plasma analysis demonstrated significantly increased systemic levels of KC/GRO, IL-6 and AGP in the blood of injured rats, already few hours following the injury. In conclusion, a rapid pro-inflammatory response, both locally and systemically, characteristic of innate immunity, was demonstrated following an induced knee joint bleed in the HA rat. Results reveal a more comprehensive inflammatory picture than previously shown, with resemblance to human hemophilic arthropathy.
2017-12-01 | GSE85051 | GEO
Project description:<p><strong>PURPOSE:</strong> Olfactory dysfunction (OD) is a debilitating symptom frequently reported by patients with chronic rhinosinusitis (CRS) and it is associated with a dysregulated sinonasal inflammation. However, little information is available about the effect of the inflammation-related nasal microbiota and related metabolites on the olfactory function in these patients. Therefore, the current study aimed to investigate the nasal microbiota-metabolites-immune interactions and their role in the pathogenesis of OD in CRS patients.</p><p><strong>METHODS:</strong> 23 and 19 CRS patients with and without OD (NOD), respectively, were enrolled in the present study. The 'Sniffin' Sticks' was used to measure the olfactory function, while the metagenomic shotgun sequencing and the untargeted metabolomic profiling were performed to assess the differences in terms of the nasal microbiome and metabolome between the two groups. The levels of nasal mucus inflammatory mediators were investigated by a multiplex flow Cytometric Bead Array (CBA).</p><p><strong>RESULTS:</strong> A decreased diversity in the nasal microbiome from the OD group compared to the NOD group was evidenced. The metagenomic analysis revealed a significant enrichment of <em>Acinetobacter johnsonii</em> in the OD group, while <em>Mycoplasma arginini</em>, <em>Aeromonas dhakensis</em> and <em>Salmonella enterica</em> were significantly less represented (LDA value > 3, p < 0.05). The nasal metabolome profiles were significantly different between the OD and NOD groups (P < 0.05). The purine metabolism was the most significantly enriched metabolic subpathway in OD patients compared with NOD patients (P < 0.001). The expressions of IL-5, IL-8, MIP-1alpha, MCP-1 and TNF were statistically and significantly increased in the OD group (P < 0.05). All these data, including the dysregulation of the nasal microbiota, differential metabolites and elevated inflammatory mediators in OD patients demonstrated a clear interaction relationship.</p><p><strong>CONCLUSIONS:</strong> The disturbed nasal microbiota-metabolite-immune interaction networks may be implicated in the pathogenesis of OD in CRS patients and the underlying pathophysiological mechanisms need to be further investigated in future studies.</p>
2023-05-12 | MTBLS7584 | MetaboLights
Project description:A purified spike (S) glycoprotein for SARS-COV-2 coronavirus was used to studying its effects on THP-1 macrophages, PBMCs and HUVEC cells. The S protein mediates SARS-CoV-2 entry into cells through binding to angiotensin converting enzyme 2 (ACE2) receptors. We measured viability, intracellular cytokines release, oxidative stress, pro-inflammatory markers and THP-1-like macrophage polarization. We identified an increase in apoptosis, ROS generation, MCP-1 and intracellular calcium expression in THP-1 macrophages. Furthermore, stimulation with the S protein polarizes THP-1 macrophages towards pro-inflammatory futures with an increase in TNFα and MHC-II M1-like phenotype markers. Treatment of cells with an ACE inhibitor, perindopril at 100nM reduced apoptosis, ROS and MHC-II expression. We further analyzed the sensitivity of HUVEC cells after exposure to a conditioned media (CM) of THP-1 macrophages stimulated with S protein. CM induced endothelial cell apoptosis and MCP-1 expression. Treatment with perindopril reduced these effects. However, direct stimulation of HUVEC cells with S protein slightly increased HIF1α and MCP-1 expression which was significantly exaggerated by ACE inhibitor treatment. S protein stimulation induced ROS generation and changed mitogenic responses of PBMCs through upregulation of TNFα and IL-17 cytokine expressions. These effects were blunted by perindopril (100nM) treatment. Proteomic analysis of S protein stimulated THP-1 macrophages with or without perindopril (100nM) uncovered more than 400 differentially regulated proteins. Our results provide a mechanistic analysis suggesting that blood and vascular component could be activated directly through S protein systemically present in circulation and that activation of local renin angiotensin system might be partially involved in this process.
2021-11-16 | PXD025516 | Pride