Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA107681 | ENA |
REPOSITORIES: ENA
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Project description:Changes of genome-wide mRNA transcription levels of human ciliary smooth muscle (hCSM) cells were determined by treating hCSM cells in culture with 200 nM of either an prostaglandin E2 receptor subtype EP2 or subtype EP4 selective agonist for 6 hours in comparison to untreated controls. This was followed by competitive hybridization of fluorescent Cy3 or Cy5 labeled cRNA probes derived from the treated versus untreated control total RNA samples onto an Agilent Human Whole Genome Expression oligonucleotide microarray. Log 2 (LN) of the intra-slide ratios (RATIO, PRE_VALUE) of treated versus untreated samples was reported as VALUE in the sample files. Keywords: prostaglandin E2 receptor agonists, subtype EP2, subtype EP4, hCSM
2008-02-24 | GSE10621 | GEO
Project description:While the role of prostaglandin E2 (PGE2) in promoting malignant progression is well-established, how to optimally block the activity of PGE2 signaling remains to be demonstrated. Clinical trials with prostaglandin pathway targeted agents have shown activity but without sufficient significance or dose-limiting toxicities that have prevented approval. PGE2 signals through four receptors (EP1-4) to modulate tumor progression. EP2 and EP4 signaling exacerbates tumor pathology and is immunosuppressive through potentiating cAMP production. EP1 and EP3 signaling has the opposite effect through increasing IP3 and decreasing cAMP. Using available small molecule antagonists of single EP receptors, the COX-2 inhibitor celecoxib, or a novel dual EP2/EP4 antagonist generated in this investigation, we tested which approach to block PGE2 signaling optimally restored immunologic activity in mouse and human immune cells and antitumor activity in syngeneic, spontaneous and xenograft tumor models. We found that dual antagonism of EP2 and EP4 together significantly enhanced the activation of PGE2-suppressed mouse and human monocytes and CD8+ T cells in vitro as compared to single EP antagonists. CD8+ T cell activation was dampened by single EP1 and EP3 antagonists. Dual EP2/EP4 PGE2 receptor antagonists increased TME lymphocyte infiltration and significantly reduced disease burden in multiple tumor models, including in the adenomatous polyposis coli (APC)min+/- spontaneous colorectal tumor model, compared to celecoxib. These results support a hypothesis that redundancy of EP2 and EP4 receptor signaling necessitates a therapeutic strategy of dual blockade of EP2 and EP4. Here we describe TPST-1495, a first-in-class orally available small molecule dual EP2/EP4 antagonist.
2023-08-21 | GSE229806 | GEO
Project description:Changes of genome-wide mRNA transcription levels of human ciliary smooth muscle (hCSM) cells were determined by treating hCSM cells in culture with 200 nM of either an prostaglandin E2 receptor subtype EP2 or subtype EP4 selective agonist for 6 hours in comparison to untreated controls. This was followed by competitive hybridization of fluorescent Cy3 or Cy5 labeled cRNA probes derived from the treated versus untreated control total RNA samples onto an Agilent Human Whole Genome Expression oligonucleotide microarray. Log 2 (LN) of the intra-slide ratios (RATIO, PRE_VALUE) of treated versus untreated samples was reported as VALUE in the sample files. Experiment Overall Design: Human Ciliary Smooth Muscle Cell Culture: Experiment Overall Design: Human ciliary smooth muscle (hCSM) cells were isolated from a female donor, received from the San Diego Eye Bank® (San Diego, CA) and cultured in DMEM with 10% fetal bovine serum and 0.5% penicillin/streptomycin according to the method reported previously by Woldemussie et al. Experiment Overall Design: For transcriptome analysis, cells were used for experiments starting at passage 4. Three independent experiments at consecutive cell passages were performed. For each experiment 0.6 x 106 cells were plated onto 15 cm dishes in MEM D-Valine medium (PromoCell, Germany) supplemented with 10% FCS, L-glutamine and antibiotics/antimycotics. Cells were grown to ~80% confluency for 6 days, followed by starvation in absence of FCS and presence of 100 nM of the cyclooxygenase inhibitor indomethacin, 20 µg/ml fatty acid-free BSA and 4 µg/ml transferrin for 17 hours. Cells were then exposed for 6 hours to 200 nM of either the EP2 agonist AGN210937 or the EP4 agonist AGN202280 (Allergan, Irvine, CA) or the corresponding amount of DMSO in the absence of FCS and presence of transferrin. Experiment Overall Design: Total RNA Extraction: Experiment Overall Design: Total RNA was isolated using a RNA isolation kit (RNAqueous; Ambion, USA) which was followed by DNase I treatment (Turbo DNA-free; Ambion) and purification, according to the manufacturerâ??s protocols. RNA was quantitated using a spectrophotometer ND-1000 (Nanodrop Technologies, USA). RNA quality was assessed regarding purity and stability using a Bioanalyser 2100 (Agilent Technologies, USA). Extracted total RNA aliquots were snap-frozen in liquid nitrogen and stored at -800C for single use. Experiment Overall Design: cRNA Labelling and Oligonucleotide Microarray Hybridization: Experiment Overall Design: Total RNA was linearly amplified and labelled with Cy3 or Cy5 using a low RNA input Fluor Linear Amp Kit (Agilent Technologies, USA). Internal RNA controls from Agilentâ??s RNA Spike-in Kit were included, comprised of mixtures of 11 in vitro synthesized transcripts derived from the Adenovirus E1A transcriptome at various ratios. The final cRNA concentration of 500 ng total RNA used was typically 590-650 ng/μl and the Cy3- or Cy5-cytidine incorporation was 5.4 -6.0 pmol/μg cRNA as determined using the Nanodrop spectrophotometer ND-1000. Experiment Overall Design: 3.5 μg of Cy3 and Cy5 labeled cRNA (treated vs. untreated samples) were competitively hybridized to high-density DNA arrays from Agilent Technologies (Whole Human Genome Oligo Microarray 44K) for 17 hours at 650C according to the manufacturerâ??s protocol. Each set of three microarray experiments for triplicate analysis contained one dye swap experiment. All microarrays were scanned and the intensities normalized over background as well as to eliminate signal intensity-dependent bias from the ratio of the two channels (Lowess normalization) using a microarray scanner from Agilent Technologies including proprietary software. All microarray data sets were imported into the microarray data analysis software Genespring 7.3 (Agilent Technologies) followed by comparison of normalized intensities. Gene identities were updated according to Agilentâ??s latest list of gene annotations (G4112F, 07Feb07). Experiment Overall Design: Consistency of microarray data quality was assessed by monitoring performance of the spiked internal RNA controls (330 microarray spots/array) at various ratios (Supplementary Data, Fig. S1), by carrying out a global analysis of all absolute fluorescent intensity values, and by analysis of negative control spots (314 microarray spots/array) for determination of detection thresholds.
2008-04-07 | E-GEOD-10621 | biostudies-arrayexpress
Project description:The EP4 receptor is known to mediate the protective effect of prostaglandin (PG) E2 in the gastrointestinal tract; however, the exact role of epithelial EP4 in intestinal pathophysiology remains unknown. We investigated the role of epithelial EP4 in maintaining colonic homeostasis by characterizing the intestinal epithelial cell-specific EP4 knockout (EP4 cKO) mice. We found a significant enrichment of genes involved in apoptosis-related pathways in the EP4 cKO colons. Moreover, inflammation-associated pathways were highly enriched and revealed more than half of the top 20 pathways related to immune response.
2019-10-29 | GSE135859 | GEO
Project description:Microglial response to Aβ and prostaglandin-E2 EP4 receptor activation
| PRJNA240243 | ENA
Project description:Wild type tumor cells, producing high levels of prostaglandin E2 (MCG101, EP2 +/+), were inoculated on EP2 knockout (EP2 -/-) and EP2 wild type (EP2 +/+) mice. Solid tumors were dissected into tumor- and tumor-stroma tissue compartments for RNA expression microarray screening, followed by metabolic pathway analyses. The study aims to evaluate simultaneous gene pathway expressions in separate tissue compartments, such as isolated tumor tissue and tumor stroma respectively.
2022-05-25 | GSE193098 | GEO
Project description:T cell-intrinsic prostaglandin E2-EP2/EP4 signaling is critical in pathogenic Th17 cell-driven inflammation
| PRJNA703988 | ENA
Project description:In vivo response of microglia to Aβ and prostaglandin-E2 EP2 receptor signaling
| PRJNA245856 | ENA
Project description:To examine the effects of prostaglandin E2/EP4 signaling on bovine CD4+ T cells, CD4+ T cells were isolated from bovine peripheral blood mononuclear cells. Isolated CD4+ T cells were cultured with anti-bovine CD3 and anti-bovine CD28 monoclonal antibodies. Following 18 hours of incubation, the cultures were incubated with EP4 agonist or DMSO, a vehicle control for 4 hours. After incubation, the cells were collected and microarray analysis was performed.
2020-11-20 | E-MTAB-9576 | biostudies-arrayexpress
Project description:Prostaglandin E2 receptor EP4-expressing macrophages promote intestinal epithelial barrier regeneration upon inflammation
| PRJNA664831 | ENA