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Screening of target genes for the drug histamine.

ABSTRACT: To explore histamine target genes,we used CRISPR-PoolTMKOUT-Human-Single vector to build GeCKO(genome-scale CRISPR-Cas9 knockout) human library.Then Genome-wide CRISPR screen was used to detect target genes in cholangiocarcinoma cells.

ORGANISM(S): Homo sapiens

PROVIDER: GSE214531 | GEO | 2025/09/30

REPOSITORIES: GEO

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Screening of target genes for the drug histamine.

Project description:Screening of target genes for the drug histamine.

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Effect of histamine on human keratinocytes

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.

2013-12-01 | E-GEOD-41585 | biostudies-arrayexpress

Effect of histamine on human keratinocytes

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Effect of depletion of histamine receptor HRH1 on gene expression of histamine treated human endothelial cells

Project description:To investigate the function of histamine signal perceived by HRH1 in the regulation of endothelial angiogenic process, we knocked down HRH1 using shRNA from histamine treated endothelial cells.

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Evaluation of the impact of neoplastic histamine secretion on melanoma progression

Project description:We previously showed that transgenic enhancement of histamine production in B16-F10 melanomas strongly supports tumor growth in C57Bl/6 mice (Cancer Res, 2005 Pos et al.). In this array experiment, gene expression profiles of transgenic mouse melanomas, secreting different amounts of histamine, were compared by whole genome microarrays. Keywords: genetic modification

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Placental Gene Expression in Response to Histamine and Oxygen

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.

2017-06-01 | GSE74446 | GEO

The Hdc GC box is critical for Hdc gene transcription and histamine-mediated anaphylaxis [ATAC-Seq]

Project description:Histamine is a critical mediator of anaphylaxis, a neurotransmitter, and a regulator of gastric acid secretion. Histidine decarboxylase is a rate-limiting enzyme for histamine synthesis. However, in vivo regulation of Hdc, the gene that encodes histidine decarboxylase is poorly understood. We sought to investigate how enhancers regulate Hdc gene transcription and histamine synthesis in resting conditions and in a mouse model of anaphylaxis. H3K27 acetylation histone modification and chromatin accessibility were used to identify candidate enhancers; The enhancer activity of candidate enhancers was measured in a reporter gene assay; and the function enhancers were validated using CRISPR deletion. Deletion of the GC box, which binds to zinc finger transcription factors, in the proximal Hdc enhancer, reduced Hdc gene transcription and histamine synthesis in the mouse and human mast cell lines. Mast cells, basophils, brain cells, and stomach cells from GC box-deficient mice transcribed the Hdc gene much less than similar cells from wild-type mice and Hdc GC box-deficient mice failed to develop anaphylaxis. Our results demonstrate that the HDC GC box within the proximal enhancer in the mouse and human HDC gene is essential for Hdc gene transcription, histamine synthesis, and histamine-mediated anaphylaxis in vitro and in vivo.

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The Hdc GC box is critical for Hdc gene transcription and histamine-mediated anaphylaxis [CUT&Tag]

2023-02-23 | GSE223386 | GEO

Translation State Array Analysis of Histamine Stimulated Human Endothelial Cells

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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Allergic mediator histamine confers immunotherapy resistance in cancer patients via histamine receptor 1 on macrophage

Project description:How to revive anti-tumor immunity in cancer patients is an unmet challenge. Retrospective screening of common medications revealed that patients who took antihistamines during immunotherapy treatment had significantly improved survival. We further uncovered that histamine and histamine receptor H1 (HRH1) are frequently increased in tumor microenvironment to cause T-cell dysfunction. HRH1 activation in macrophages inhibits proinflammatory signaling and dysregulates fatty acid metabolism. HRH1 also increases membrane expression of immune checkpoint V-domain Ig suppressor of T-cell activation (VISTA) in macrophages, which renders CD8+ T-cells dysfunctional. Knockout HRH1 or antihistamine treatment negated the immunosuppressive activity of the macrophages, revitalized T-cell cytotoxic function, and restored immunotherapy response. Both animal and human data showed that allergy facilitated tumor growth and induced immunotherapy resistance via histamine/HRH1 axis, underscoring the tumor-p rone activity of allergy. These findings demonstrate that pre-existing allergy in cancer patients can dampen response to immunotherapies and warrant perspective investigation of antihistamines as an adjuvant agent for combinatorial immunotherapy.

2020-11-14 | GSE161484 | GEO

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