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Mapping Variation in Cellular and Transcriptional Response to 1,25-dihydroxyvitamin D3 in Peripheral Blood Mononuclear Cells

ABSTRACT: This study characterizes the genetic basis of variation in the immunomodulatory effects of the active form of vitamin D, 1,25-dihydroxyvitamin D3 (1,25D). This was done by mapping quantitative traits of 1,25D response both at the cellular and transcriptional level in peripheral blood mononuclear cells (PBMCs). Total RNA extraced from peripheral blood mononuclear cells from 85 healthy individuals of African-African ancestry treated with 1,25D or the vehicle control, ethanol, for 6 hours.

ORGANISM(S): Homo sapiens

SUBMITTER: Silvia Kariuki

PROVIDER: E-GEOD-82023 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Patterns of transcriptional response to 1,25-dihydroxyvitamin D3 and bacterial lipopolysaccharide in primary human monocytes

Project description:This study examines patterns of genome-wide transcriptional response to the active form of vitamin D, 1,25-dihyroxyvitamin D3 (1,25D), and the bacterial lipopolysaccharide (LPS) in primary human monocytes, to better understand pathways underlying the immunomodulatory role of 1,25D. Total RNA extraced from monocytes from 20 healthy individuals of African-African and European-American ancestry treated with 1,25D alone or in the presence of LPS for 24 hours.

2016-02-20 | E-GEOD-78083 | biostudies-arrayexpress

Mapping Variation in Cellular and Transcriptional Response to 1,25-dihydroxyvitamin D3 in Peripheral Blood Mononuclear Cells

Project description:This study characterizes the genetic basis of variation in the immunomodulatory effects of the active form of vitamin D, 1,25-dihydroxyvitamin D3 (1,25D). This was done by mapping quantitative traits of 1,25D response both at the cellular and transcriptional level in peripheral blood mononuclear cells (PBMCs).

2016-07-01 | GSE82023 | GEO

Patterns of transcriptional response to 1,25-dihydroxyvitamin D3 and bacterial lipopolysaccharide in primary human monocytes

2016-02-20 | GSE78083 | GEO

Effects of 1,25-dihydroxyvitamin D (1,25D) on global gene expression of human fibroblasts with (CO) or without (MUT) a functional VDR

Project description:Human skin fibroblasts from an individual with hereditary vitamin D-resistant rickets bearing a homozygous p.Arg30* VDR mutation [Damiani et al., Osteoporos Int 2015; 26(6):1819-23] and from an age/sex-matched control were obtained from 4-mm punch biopsies of the forearm skin, after institutional board approval and with informed consent. Skin explants were fragmented in 6-well tissue culture plates and covered in complete AmnioMAX™ C-100 medium until attachment to surface; after approximately 12 days fibroblasts grown out of explants covered well surfaces completely. Secondary fibroblast cultures were maintained in high glucose DMEM supplemented with 10% FBS and 1% P/S. Fibroblasts were used for experiments between passages five to fifteen. Global gene expression of CO and MUT fibroblasts in response to 1,25D or ethanol vehicle (Veh) was analysed using microarrays. Six independent biological replicates were performed for each experimental condition: CO Veh, CO 1,25D, MUT Veh and MUT 1,25D. Cells were grown in 6-well plates and treated with 10 nM 1,25D or ethanol (1 ul/ml of medium) for 24 hours before RNA extraction. Based on quality control of extracted RNA performed with the 2100 Bioanalyzer (Agilent Technologies, Palo Alto, CA), four samples of each condition were chosen for microarray gene expression analysis, all with RNA integrity number above 8.00. Samples were processed according to manufacturer’s instructions, starting with 200 ng total RNA. Altogether, sixteen samples of labeled fragmented cDNA were hybridized to GeneChip Human Gene 2.0 ST Arrays (Affymetrix). Array data was analysed using Partek Genomics Suite, and based on quality control one array (MUT_Veh_4) was excluded. A Benjamini-Hochberg-corrected p-value cut-off of 0.05 was used for selecting significant differentially expressed genes.

2019-02-28 | GSE127314 | GEO

1,25-dihydroxyvitamin D3 triggers an anti-inflammatory response in brain pericyte

Project description:Background: Epidemiology and experimental studies suggest 1,25-dihydroxyvitamin D3 plays a neuroprotective role in neurodegenerative diseases including Alzheimer's disease. Most of the experimental data on the genes regulated by this hormone in brain cells have been obtained with neuron and glial cells. Emerging evidence demonstrates pericyte plays a critical role in brain function that encompasses its classical function in the control and maintenance of the blood brain barrier. However, the gene response of brain pericyte to 1,25D remains to be investigated. Methods: The transcriptomic response of human brain pericytes to 1,25-dihydroxyvitamin D3 was analyzed. Results were confirmed by RT-qPCR for the genes of interest. Results: We demonstrate that human brain pericyte in culture responds to 1,25-dihydroxyvitamin D3 by regulating genes involved in the control of neuro-inflammation. We also showed that pericytes respond to the pro-inflammatory cytokines TNF-alpha and Interferon gamma by inducing the expression of the gene involved in the synthesis of 1,25-dihydroxyvitamin D3 named CYP27B1. Conclusion: Taken together these results suggest that neuro-inflammation could trigger the synthesis of 1,25-dihydroxyvitamin D3 by brain pericytes, which will in turn respond to the hormone by a global anti-inflammatory response.

2017-01-01 | GSE54765 | GEO

Gene-regulatory potential of 1α,25-dihydroxyvitamin D3

Project description:In this study, we analysed the in-vitro modulation of the transcriptome of human PBMCs isolated from 14 individuals after 24 hours of stimunation with 10 nM 1α,25-dihydroxyvitamin D3 (1,25D)

2024-03-20 | GSE261699 | GEO

Stimulation of 1,25-dihydroxyvitamin D3 production by 1,25-dihydroxyvitamin D3 in the hypocalcaemic rat.

Project description:Serum 1,25-dihydroxyvitamin D3 concentration and renal 25-hydroxyvitamin D 1 alpha-hydroxylase activity were measured in rats fed various levels of calcium, phosphorus and vitamin D3. Both calcium deprivation and phosphorus deprivation greatly increased circulating levels of 1,25-dihydroxyvitamin D3. The circulating level of 1,25-dihydroxyvitamin D3 in rats on a low-calcium diet increased with increasing doses of vitamin D3, whereas it did not change in rats on a low-phosphorus diet given increasing doses of vitamin D3. In concert with these results, the 25-hydroxyvitamin D 1 alpha-hydroxylase activity was markedly increased by vitamin D3 administration to rats on a low-calcium diet, whereas the same treatment of rats on a low-phosphorus diet had no effect and actually suppressed the 1 alpha-hydroxylase in rats fed an adequate-calcium/adequate-phosphorus diet. The administration of 1,25-dihydroxyvitamin D3 to vitamin D-deficient rats on a low-calcium diet also increased the renal 25-hydroxy-vitamin D 1 alpha-hydroxylase activity. These results demonstrate that the regulatory action of 1,25-dihydroxyvitamin D3 on the renal 25-hydroxyvitamin D3 1 alpha-hydroxylase is complex and not simply a suppressant of this system.

| S-EPMC1152329 | biostudies-other

1,25-Dihydroxyvitamin D3 Suppresses Prognostic Survival Biomarkers Associated with Cell Cycle and Actin Organization in a Non-Malignant African American Prostate Cell Line

Project description:Vitamin D3 is a steroid hormone that has been shown to prevent tumor growth in prostate cells. Not having enough vitamin D3 in the blood has been linked to advanced prostate cancer and mortality, especially in African American men. We wanted to understand how vitamin D affected pathways that keep prostate cells from becoming cancerous, which could lead to new therapeutic targets and treatments, especially for African American men who tend to be more prone to being vitamin D deficient compared to European men. Here, we studied a non-cancerous African American prostate cell line treated with the active form of vitamin D with a concentration similar to what is found in the body for 24 h. Using RNA whole-transcriptome sequencing, we compared these treated cells with untreated cells to assess genes and pathways significantly changed due to treatment. We found that vitamin D affected the activity of 1600 genes, mainly suppressing pathways linked to prostate cell movement, growth, and viability. Only two genes, ANLN and ECT2, were strongly correlated with prostate cancer prognosis. Downregulation of ANLN and ECT2 was also shown to repress signaling pathways involved in prostate cell movement, growth, malignant transformation, and viability. In further validation utilizing prostate cancer cohorts comprised of African American and European American men, patients tended to have better sur-vival rates when these genes were less active. Our results suggest that vitamin D decreases the activity of these genes and could be important for preventing prostate cancer, especially for African American men. This could lead to the development of new treatments targeting specific genes and pathways involved in prostate cancer growth.

2024-05-14 | GSE267396 | GEO

1,25-Dihydroxyvitamin-D3 Induces Avian ?-Defensin Gene Expression in Chickens.

Project description:Host defense peptides (HDPs) play a critical role in innate immunity. Specific modulation of endogenous HDP synthesis by dietary compounds has been regarded as a novel approach to boost immunity and disease resistance in animal production. 1,25-dihydroxy vitamin D3 (1,25D3) is well known as a powerful HDP inducer in humans, but limited information about the effect of 1,25D3 on HDPs in poultry is available. Here, we sought to examine whether 1,25D3 could stimulate avian ?-defensin (AvBD) expression in chickens. We used chicken embryo intestinal epithelial cells (CEIEPCs) and peripheral blood mononuclear cells (PBMCs) to study the effect of 1,25D3 on the expression of AvBDs. We observed that 1,25D3 is able to up-regulate the expression of several AvBDs in CEIEPCs and PBMCs, whereas it increased the amounts of AvBD4 mRNA in CEIEPCs only in the presence of lipopolysaccharide (LPS). On the other hand, LPS treatment not only inhibited the expression of CYP24A1 but also altered the expression pattern of VDR in CEIEPCs. Furthermore, AvBDs were not directly regulated by 1,25D3, as cycloheximide completely blocked 1,25D3-induced expression of AvBDs. Our observations suggest that 1,25D3 is capable of inducing AvBD gene expression and is a potential antibiotic alternative through augmentation of host innate immunity as well as disease control in chickens.

| S-EPMC4852925 | biostudies-literature

Gene expression data from yerba mate treated and non-treated cultured PBMCs activated with phytohemagglutinin

Project description:Yerba mate (YM) has been shown to have anti-inflammatory properties in several studies. However, this effect has been found mainly in obesity-related in inflammation. The aim of this work was to study the effect of YM in cultured peripheral blood mononuclear cells to see whether it has anti-inflammatory properties. We stimulated peripheral blood mononuclear cells in vitro with phitohemaglutinin in the presence of yerba mate and determined their activation measuring the the expression of CD25 by flow cytometry. We observed that YM treatment produced a dose-dependent reduction in PBMC activation (CD25 positive cells) when they were stimulated with PHA. This effect was also observed in T cells (CD3 positive) subpopulation. Microarray analysis revealed the differential expression of 128 genes in YM-treated cells. According to a protein-protein interaction database, these genes were highly connected and they are involved in inflammatory response. In summary, it was demonstrated that YM produces a reduction in the amount of activated cells under the stimulation of PHA. Therefore, it might be used in diseases with an inflammatory component. PBMC samples from a healthy individual were cultured and stimulated with phytohemagglutinin. Gene expression of yerba mate treated and non-treated cells was analyzed in duplicates, having in total four microarrays.

2016-08-15 | E-GEOD-84407 | biostudies-arrayexpress

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