Similar Datasets
Project description:The goal of this study was the identification of a novel mode of action for this unmet need. Pharmacological tool compounds: suberoylanilide hydroxamic acid (SAHA) and tadalafil, targeting histone deacetylases (HDAC) and phosphodiesterase 5 (PDE5) respectively, were utilized simultaneously for in-vitro and in-vivo Proof-of-Concept (PoC). A synergistic effect was observed in the amelioration of AD signs using the combination therapy in Tg2576 mice. Finally, a therapeutic agent, CM-414, inhibiting simultaneously HDAC2/6 and PDE5 was generated and tested in Tg2576 mice. CM-414 reversed cognitive impairment, reduced amyloid and tau pathology, and rescued dendritic spine density loss in the hippocampus in AD mice. Importantly, the effect obtained was present after a 4-weeks wash-out period.However, to obtain a compound with a safer profile we designed a new compound, CM-695, targeting HDAC6 and PDE9. CM-695 showed similar effect to that of CM-414 after chronic administration to Tg2576 although the effect was not mantained when CM-695 was no longer administered.
2019-07-16 | GSE128422 | GEO
Project description:We showed that co-culture with TAMs triggered Bmi1 expression in gastrointestinal cancer cell lines. miRNAs have been found to target various oncogenes and tumor suppressors. We therefore hypothesized that the regulation of Bmi1 expression in gastrointestinal cancer cells may be mediated by miRNAs using miRNA microarray analysis. THP-1 cells were seeded in the transwell inserts (3540, Corning) for 6-well plates (1 M-CM-^W 106 cells/well). For preparation of M1-polarized THP-1 macrophages, 320 nM phorbol myristate acetate (PMA) was added to THP-1 cells for 6 h, followed by PMA plus 20 ng/ml interferon (IFN)-M-NM-3 and 100 ng/ml lipopolysaccharide for the following 18 h. For preparation of M2-polarized THP-1 macrophages, 320 nM PMA was added to THP-1 cells for 6 h, followed by PMA plus 20 ng/ml interleukin (IL)-4/IL-13 for the following 18 h. After three washes to remove cytokines, M1- or M2-polarized THP-1 macrophages were co-cultured in upper inserts with AGS cells in 6-well plates (1 M-CM-^W 105 cells/well) without direct contact, in each medium without 10% FBS as described above. After 24 h of co-culture, the upper inserts containing macrophages were discarded. AGS cells were collected and analyzed to identify downregulated microRNA in a gastric cancer cell line co-cultured with M1- or M2-polarized macrophage.
2013-09-05 | E-GEOD-50601 | biostudies-arrayexpress
Project description:Psoriasis and atopic dermatitis (AD) are characterized by polarized CD4+ T cell responses. During the polarization of naM-CM-/ve CD4+ T cells, DNA methylation plays an important role in the regulation of gene transcription. In this study, we profiled the genome-wide DNA methylation status of naM-CM-/ve CD4+ T cells in patients with psoriasis or AD and healthy controls using a ChIP-seq method. As a result, twenty-six regions in the genome ranging in size from 10 to 70 kb were markedly hypomethylated in patients with psoriasis. These regions were mostly pericentromeric on 10 different chromosomes and overlapped with various strong epigenomic signals, such as histone modifications and transcription factor binding sites, that were observed in the ENCODE project. Gene-centric analysis indicated that the promoter regions of 124 genes on the X chromosome had dramatically elevated methylation levels in patients with psoriasis as compared to those from healthy controls (> 4-fold). Moreover, immune-related genes on the X chromosome had higher hypermethylation than other genes (P < 0.05). These findings imply that methylation changes in naM-CM-/ve CD4+ T cells may affect CD4+ T cell polarization, especially in the pathogenesis of psoriasis. Keywords: Psoriasis, Atopic dermatitis, DNA methylation, naM-CM-/ve CD4+ T cells Sample submission examines DNA methylation from human naive CD4+ T cells in patients with psoriasis and atopic dermatitis. Note: Raw data available only for Sample GSM871288.
2012-03-17 | E-GEOD-35582 | biostudies-arrayexpress
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
Project description:Using microarray analysis, we explored the differences in gene expression profiles between individual and combined stimulation of Toll-like receptor 4 (TLR4) and Nucleotide oligomerization domain (NOD)-like receptor (NOD2) in THP-1 cells. Analysis was performed 3 hours post addition of TLR4 agonist MPLA and the NOD2 agonist MDP to THP-1 cells. The results provide the detailed molecular profile of the the genetic response to individual and combined stimulation of TLR4 and NOD2 receptors THP-1 cells (Invivogen) were seeded in 3-cm culture dishes at 1x10^6 cells per dish in RPMI medium. Next day, cells were treated with MDP (20μg/ml) and MPLA (1μg/ml) individually or in combination or left untreated.
2016-04-05 | E-GEOD-79900 | biostudies-arrayexpress
Project description:Cytoplasmic localization of proline, glutamic acid, leucine-rich protein 1 (PELP1) is observed in ∼40% of women with invasive breast cancer. In mouse models, PELP1 overexpression in the mammary gland leads to premalignant lesions and eventually mammary tumors. In preliminary clinical studies, cytoplasmic localization of PELP1 was seen in 36% of women at high risk of developing breast cancer. Here, we investigated whether cytoplasmic PELP1 signaling promotes breast cancer initiation in models of immortalized human mammary epithelial cells (HMECs). Global gene expression analysis was performed on HMEC lines expressing vector control, PELP1-wt, or mutant PELP1 in which the nuclear localization sequence was altered, resulting in cytoplasmic localization of PELP1 (PELP1-cyto). Global gene expression analysis identified that PELP1-cyto expression in HMECs induced NF-κB signaling pathways. Western blotting analysis of PELP1-cyto HMECs showed up-regulation of inhibitor of κB kinase ϵ (IKKϵ) and increased phosphorylation of the NF-κB subunit RelB. To determine whether secreted factors produced by PELP1-cyto HMECs promote macrophage activation, THP-1 macrophages were treated with HMEC-conditioned medium (CM). PELP1-cyto CM induced changes in THP-1 gene expression as compared with control cell CM. Double conditioned medium (DCM) from the activated THP-1 cells was then applied to HMECs to determine whether paracrine signaling from PELP1-cyto-activated macrophages could in turn promote migration of HMECs. PELP1-cyto DCM induced robust HMEC migration, which was reduced in DCM from PELP1-cyto HMECs expressing IKKϵ shRNA. Our findings suggest that cytoplasmic localization of PELP1 up-regulates pro-tumorigenic IKKϵ and secreted inflammatory signals, which through paracrine macrophage activation regulates the migratory phenotype associated with breast cancer initiation.
2017-01-31 | GSE81447 | GEO
Project description:Considering the numerous complex and different pathological mechanisms involved in Alzheimer´s disease (AD) progression, treatments targeting a single cause may lead to limited benefits. The goal of this study was the identification of a novel mode of action for this unmet need. Pharmacological tool compounds: suberoylanilide hydroxamic acid (SAHA) and tadalafil, targeting histone deacetylases (HDAC) and phosphodiesterase 5 (PDE5) respectively, were utilized simultaneously for in-vitro and in-vivo Proof-of-Concept (PoC). A synergistic effect was observed in the amelioration of AD signs using the combination therapy in Tg2576 mice. Finally, a therapeutic agent, CM-414, inhibiting simultaneously HDAC2/6 and PDE5 was generated and tested in Tg2576 mice. CM-414 reversed cognitive impairment, reduced amyloid and tau pathology, and rescued dendritic spine density loss in the hippocampus in AD mice. Importantly, the effect obtained was present after a 4-weeks wash-out period.
2015-11-27 | GSE62240 | GEO
Project description:The accumulation of amyloid-ß (Aß) peptides in the brain is a crucial step in the pathogenesis of Alzheimer`s disease (AD). Several studies indicate that microglia cells in the brain have the ability to internalize Aß by phagocytosis and might therefore play a protective role in AD. However, the mechanisms underlying Aß clearance remain unresolved. We have found that small molecule inhibitors of the ubiquitous glycogen synthase kinase 3ß (GSK3ß) stimulate the uptake of Aß by human THP-1 monocytes and primary murine microglia cells. To investigate how GSK3ß inhibitors might stimulate Aß uptake, we conducted microarray-based gene expression analyses of THP-1 cells after treatment with three different GSK3ß inhibitors. We identified a subset of genes similarly altered by all three inhibitors, including chemokines and surface receptors that have been linked to the regulation of microglial activation and phagocytosis.
2020-11-30 | GSE85238 | GEO
Project description:Deep RNA sequencing analysis revealed that compared to control (no cold storage/ischemia), 6h-cold storage led to 266 differentially expressed genes, many of which were implicated in modulating mitochondrial performance, oxidative stress response, myocardial function, and apoptosis. Either bone marrow- (BM) or adipose tissue-derived (Ad) mesencymal stromal cell conditioned medium (MSC-CM) restored these gene expression towards control.
2022-07-20 | GSE208341 | GEO
Project description:THP-1 is a representative leukemia cell line, and has been widely used all around the world since its establishment in Japan in 1980. Differences in THP-1 cells have been reported; however, the THP-1 genomes have not been accurately characterized.
2021-08-31 | GSE178731 | GEO