Effect of depletion of histamine receptor HRH1 on gene expression of histamine treated human endothelial cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE211726 | GEO | 2022/08/28
REPOSITORIES: GEO
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Project description:Although immune checkpoint blockade (ICB) therapy has proven to be extremely effective in managing certain cancers, its efficacy in pancreatic ductal adenocarcinoma (PDAC) remains limited. Previous studies have indicated that histamine and histamine receptor H1 (HRH1) can suppress immunity by affecting immune cells. This study uncovered an unexplored role of HRH1 intrinsic to tumor cells in PDAC. When HRH1 specific to tumor cells was inhibited in PDAC mouse models, there was a noticeable increase in MHC-I expression in these cells via the activation of cholesterol biosynthesis signaling. This augmented the infiltration and efficacy of cytotoxic CD8+ T cells, synergizing anticancer immunity and mitigating resistance to ICB treatment. Our results highlight that HRH1 plays an immunosuppressive role in cancer cells. Consequently, HRH1 intervention may be a promising method to amplify the responsiveness of PDAC to immunotherapy.
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Project description:Confluent human umbilical vein endothelial cells (HUVECs) were exposed to histamine (100 mM) for 2 hours. Ribosomal profiling via gradient centrifugation and fractionation was used to separate monosome, or under-translated, and polysome, or actively translated, mRNA species that were then used to probe cDNA arrays, a process known as Translation State Array Analysis (TSAA). Four samples were obtained from these experiments, control monosome, control polysome, histamine monosome and histamine polysome. Using the normalized signal intensities from the GeneFilters, we calculated a translation index, or measure of movement of an mRNA molecule from the monosome to the polysome fraction upon stimulation. This calculation was made as follows: (histamine polysome/histamine monosome)/(control polysome/control monosome). Translational indices greater than 2.5 (upregulated) or lower than 0.4 (downregulated) were chosen for further study. Keywords: Translation State Array Analysis
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Project description:Endothelial cells (HUVEC) were treated with histamine, the endogenous ligand of histamine receptors, for a global overview of its cellular effects. Changes of the intracellular and secreted proteomes were analyzed using shotgun proteomics. Furthermore, a selected set of proteins was quantified using parallel reaction monitoring.
2017-02-28 | MSV000080587 | MassIVE
Project description:Maternal Blood histamine levels are tightly controlled in normal pregnancy. However, in specific complications of human pregnancy such as pre-eclampsia the levels of both placental and maternal blood histamine increase. Increasing blood histamine levels nonetheless, have been associated with oxidative stress, endothelial dysfunction, abnormal tissue growth, and Th1/TH2 imbalance, which are also linked to pre-eclampsia. Little is known of the molecular responses in the placenta to the prolonged exposure to increasing histamine levels in the presence of changing oxygen concentrations. We used microarray to detail the global programme of placental gene expression in response to histamine and oxygen and identified distinct classes of regulated genes underlying the molecular functions of histamine in the placenta.
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Project description:Confluent human umbilical vein endothelial cells (HUVECs) were exposed to histamine (100 mM) for 2 hours. Ribosomal profiling via gradient centrifugation and fractionation was used to separate monosome, or under-translated, and polysome, or actively translated, mRNA species that were then used to probe cDNA arrays, a process known as Translation State Array Analysis (TSAA). Four samples were obtained from these experiments, control monosome, control polysome, histamine monosome and histamine polysome. Using the normalized signal intensities from the GeneFilters, we calculated a translation index, or measure of movement of an mRNA molecule from the monosome to the polysome fraction upon stimulation. This calculation was made as follows: (histamine polysome/histamine monosome)/(control polysome/control monosome). Translational indices greater than 2.5 (upregulated) or lower than 0.4 (downregulated) were chosen for further study. HUVECs were stimulated with histamine (100 mM) for 2 hours. Cycloheximide (CHX) was added to a final concentration of 100 ng/mL for 5 minutes and cells were then rinsed with cold HBSS containing CHX (100 ng/mL) and scraped from the dish and pelleted by centrifugation (2000 x g, 5 minutes). The supernatant was removed and cells were carefully resuspended in 375 ïL Low Salt Buffer (LSB; 20 mM Tris, 10 mM NaCl, 3 mM MgCl2, pH 7.4) + RNasin (40 U/mL) + DTT (10 nM) for 3 minutes on ice. 125 ïL LSB Lysis buffer (LSB containing 200 mM sucrose and 1.2% Triton-X100) was then added and cells disrupted by pipetting. The mixture was then transferred to 1.7 mL microfuge tubes and centrifuged (20,000 x g, 1 minute, 4ï° C) to remove nuclei and cellular debris. The supernatant was transferred to a new tube containing 50 ïL LSB + RNasin (40 U/mL) + DTT (10 nM) and 15 ïL 5M NaCl. This mixture was then layered onto prepoured gradients (15-50% sucrose in LSB). Gradients were spun at 43,700 rpm for 90 minutes (4ï° C) and then run on a density gradient flow cell fractionator (Isco) to obtain ribosomal profiles. Ribosomal fractions corresponding to monosomes (M) and polysomes (P) (Figure 1) were collected into Trizol LS (Invitrogen) and total RNA isolated according to the directions of the manufacturer. Total RNA was reverse transcribed using oligo dT primers in the presence of 33P dCTP to generate labeled cDNA probes from the M and P associated mRNA fractions of control and stimulated cells and these probes used to detect specific array elements on four identical Research Genetics (ResGen) Named Human Gene cDNA GeneFilters (GF 211, Invitrogen). These filters were washed using high stringency conditions and exposed to phosphorimaging screens for analysis using Pathways 3, proprietary software included with the ResGen filters. Hybridization signals were normalized to the average intensity of the hybridization signals from the particular array filter to correct for differing global hybridization efficiencies between filters. To determine if a particular hybridization signal was significantly above background levels, an initial screen of the array elements was conducted by dividing the hybridization signal of an individual cDNA spot by the background signal on particular filter. Background signal levels were determined using the Pathways 3 analysis software that measures the signal intensity of the area between cDNA spots and averages that signal over the area of the entire array. Array elements were considered to be distinguishable from background if the hybridization signal/background ratio was greater than 1.1. Signal intensities from each filter were normalized by dividing the raw signal intensity of the cDNA spot by the average signal intensity for the entire filter. The translation state (TS) of each qualifying array element was determined by dividing the normalized signal intensity of the element in the polysome fraction by the normalized signal intensity of the element in the monosome fraction: TS=P/M. The Translation Index (TLI), a measure of the change of translation states of individual genes, was determined by calculating the ratio of the treated cell TS to the control cell TS; TLI = TSe/TSc where e represents experimental or treated conditions and c represents controls. In this scenario, a gene that is not regulated by translation would have a TLI value of 1, actively translated genes would have a TLI value greater than 1, whereas a poorly translated or under-translated gene would have a TLI value less than 1. Arbitrary TLI values of 2.5 and 0.4 were used to categorize individual array elements as being translationally regulated.
2010-07-01 | E-GEOD-5385 | biostudies-arrayexpress
Project description:Genome-wide analysis of gene expression after stimulation with histamine to assess the main processes, molecular functions and cellular components affected as well as genes related to skin barrier function. HaCaT cells were exposed to histamine (1ug/ml) for 24h. The cells were lysed, total RNA was extracted and microarray study was performed on Illumina HT12 platform.
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Project description:Smoking is associated with increased airway histamine responsiveness and elevated histamine levels. Transcript levels of histidine decarboxylase (HDC; histamine synthesis) and histamine N-methyltransferase (HNMT; histamine degradation) were evaluated in small airway epithelial (SAE) cells obtained from smokers or non-smokers. Histamine+ SAE cells increased in smokers compared to nonsmokers (p< 0.03). HDC transcript levels were elevated in smokers compared with non-smokers when comparing both bulk RNA from SAE (p< 0.03) and single cell HDC transcripts in mast cells (p<10-6). Elevated HDC transcript levels in mast cells corre-lated with elevated IL33 transcript levels in smoker SAE basal cells, and elevated transcript levels of the IL33 receptor, IL1RL1, in mast cells. In contrast to HDC, transcript levels of HNMT were decreased (p<10-4) in smoker SAE. Significant decreases in HNMT transcript levels were found broadly across SAE differentiated cell types. An in vitro SAE culture model treated with cigarette smoke extract reduced HNMT transcript levels (p<0.05). Together, the data suggests that smoking results in an accumulation of mast cells, elevated expression of histamine-synthesizing mast cell HDC, and a decrease in histamine-degrading HNMT transcript levels broadly in the epithelium. These smoking induced changes are likely contributors to elevated histamine levels in the airways of smokers.
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Project description:Genome-wide analysis of gene expression after stimulation with histamine to assess the main processes, molecular functions and cellular components affected as well as genes related to skin barrier function.
2013-12-01 | GSE41585 | GEO