Regulation of mRNA expression of monocytic cells by stimulation with pro- abd anti-inflammatory eicosanoids
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE8928 | GEO | 2008/07/31
SECONDARY ACCESSION(S): PRJNA102341
REPOSITORIES: GEO
Similar Datasets
Project description:Eicosanoids are potent regulators of gene expression of inflammatory cells. Pro- (leukotrienes B4 and C4) and anti-indflammatory (lipoxins A4 and B4) eicosanoids have been described in the literature but the detailed impact of these lipid mediators on the gene expression pattern of monocytic cells has not been studied in detail. We cultured the permanent monocytic cell line MonoMac 6 for 12 h in the absence (solvent control) and presence of these eicosanoids and quantified the differential gene expression patterns using the microarray technology. Experiment Overall Design: MonoMac6 cells were grown according to the recommendations of the German Tissue and Cell Culture Collection (Braunschweig) to near confluency. Then 100 nM of the eicosanoids (leukotriene B4, leukotriene C4, lipoxin A4, lipoxin B4) were added to the culture medium as DMSO stock solution and the cells were further cultured for 12 h with the stimuli. Then the cells were harvested, washed and total RNA was extracted according to the Qiagen protocol. Total RNA was used for microarray hybridization.
2008-10-20 | E-GEOD-8928 | biostudies-arrayexpress
Project description:Introduction: Placental infection and inflammation are risk factors for adverse pregnancy outcomes, including preterm labor. However, the mechanisms underlying these outcomes are poorly understood. Methods: To study this response, we have employed a pregnant mouse model of placental infection caused by the bacterial pathogen Listeria monocyogenes, which infects the human placenta. Through in vivo bioluminescence imaging, we confirm the presence of placental infection and quantify relative infection levels. Infected and control placentas were collected on embryonic day 18 for RNA sequencing to evaluate gene expression signatures associated with infection by Listeria. Results: We identified an enrichment of genes associated with eicosanoid biosynthesis, suggesting an increase in eicosanoid production in infected tissues. Because of the known importance of eicosanoids in inflammation and timing of labor, we quantified eicosanoid levels in infected and uninfected placentas using semi-targeted mass spectrometry. We found a significant increase in the concentrations of several key eicosanoids: leukotriene B4, lipoxin A4, prostaglandin A2, prostaglandin D2, and eicosatrienoic acid. Discussion: Our study provides a likely explanation for dysregulation of the timing of labor following placental infection. Further, our results suggest potential biomarkers of placental pathology and targets for clinical intervention.
2022-04-21 | GSE201038 | GEO
Project description:2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a potent aryl hydrocarbon receptor (AhR) agonist that elicits a broad spectrum of dose-dependent effects in the liver, including hepatic lipid accumulation coupled with inflammation. To determine the role of inflammatory lipid mediators in TCDD-mediated hepatotoxicity, eicosanoid metabolism was investigated in female Sprague-Dawley (SD) rats. Rats were gavaged with sesame oil vehicle or 0.01-10 µg/kg TCDD every 4 days for 28 days. Hepatic RNA-Seq data from female SD rats was compared with data from female C57BL/6 mice and functionally annotated to determine key toxicogenomic differences between the two species regarding TCDD exposure. Hepatic RNA-Seq data from female SD rats integrated with untargeted metabolomics of liver, serum, and urine identified dose-dependent changes in linoleic acid (LA) and arachidonic acid (AA) metabolism. TCDD also elicited dose-dependent differential gene expression associated with cyclooxygenase, lipoxygenase, and cytochrome P450 epoxidation/ hydroxylation pathways with corresponding changes in omega-6 (e.g. AA and LA) and omega-3 polyunsaturated fatty acids (PUFAs) as well as their eicosanoid metabolites. Overall, total omega-6 PUFAs increased, while total omega-3 PUFAs decreased. Phospholipase A2 (Pla2g12a) was induced 6-fold consistent with increased AA metabolism, while AA utilization by lipoxygenases Alox5 (2-fold) and Alox15 (10-fold) increased leukotrienes (LTs), important mediators signaling an inflammatory response. More specifically, TCDD increased pro-inflammatory eicosanoids, including leukotriene (LT) B4 (3-fold), and LTB3 (5-fold), known signals for the recruitment of neutrophils to areas of tissue damage. Dose-response modeling of metabolite and gene expression changes suggests the cytochrome P450 hydroxylase/epoxygenase and the lipoxygenase pathways are the most sensitive to TCDD. While several differentially expressed genes (DEGs) associated with eicosanoid biosynthesis contained putative dioxin response elements (pDRE) within their regulatory region, ChIP-Seq analysis showed little AhR enrichment, suggesting TCDD-elicited induction of eicosanoid biosynthesis is not a direct effect of AhR activation.
2018-12-01 | GSE110293 | GEO
Project description:2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a potent aryl hydrocarbon receptor (AhR) agonist that elicits a broad spectrum of dose-dependent effects in the liver, including hepatic lipid accumulation coupled with inflammation. To determine the role of inflammatory lipid mediators in TCDD-mediated hepatotoxicity, eicosanoid metabolism was investigated in female Sprague-Dawley (SD) rats. Rats were gavaged with sesame oil vehicle or 0.01-10 µg/kg TCDD every 4 days for 28 days. Hepatic RNA-Seq data from female SD rats was compared with data from female C57BL/6 mice and functionally annotated to determine key toxicogenomic differences between the two species regarding TCDD exposure. Hepatic RNA-Seq data from female SD rats integrated with untargeted metabolomics of liver, serum, and urine identified dose-dependent changes in linoleic acid (LA) and arachidonic acid (AA) metabolism. TCDD also elicited dose-dependent differential gene expression associated with cyclooxygenase, lipoxygenase, and cytochrome P450 epoxidation/ hydroxylation pathways with corresponding changes in omega-6 (e.g. AA and LA) and omega-3 polyunsaturated fatty acids (PUFAs) as well as their eicosanoid metabolites. Overall, total omega-6 PUFAs increased, while total omega-3 PUFAs decreased. Phospholipase A2 (Pla2g12a) was induced 6-fold consistent with increased AA metabolism, while AA utilization by lipoxygenases Alox5 (2-fold) and Alox15 (10-fold) increased leukotrienes (LTs), important mediators signaling an inflammatory response. More specifically, TCDD increased pro-inflammatory eicosanoids, including leukotriene (LT) B4 (3-fold), and LTB3 (5-fold), known signals for the recruitment of neutrophils to areas of tissue damage. Dose-response modeling of metabolite and gene expression changes suggests the cytochrome P450 hydroxylase/epoxygenase and the lipoxygenase pathways are the most sensitive to TCDD. While several differentially expressed genes (DEGs) associated with eicosanoid biosynthesis contained putative dioxin response elements (pDRE) within their regulatory region, ChIP-Seq analysis showed little AhR enrichment, suggesting TCDD-elicited induction of eicosanoid biosynthesis is not a direct effect of AhR activation.
2018-12-01 | GSE110282 | GEO
Project description:Monocytic U937 cell lines and crosslinked CD32 & CD64 at different time points Keywords: time-course
2009-07-20 | GSE1537 | GEO
Project description:During stress, while global mRNA translation is reduced, specific stress-responsive transcripts are translated. How stress-responsive mRNAs are selectively translated is unknown. Ribosome modifications may facilitate selective translation of specific transcripts in different cell types under differing conditions. Here we identify METL-5 as a C. elegans N6-adenosine methyltransferase that methylates adenosine 1717 on 18S rRNA. METL-5 specifically enhances ribosomal binding and selective translation of a cytochrome P450 mRNA, cyp-29A3, whose protein product oxidizes the omega-3 polyunsaturated fatty acid (PUFA) eicosapentaenoic acid to eicosanoids, important signaling molecules in stress responses. In fact although mutant metl-5 C. elegans grow normally under homeostatic conditions, they are resistant to a variety of stresses, including heat shock, cold, oxidants and UV irradiation. metl-5 mutant worms have reduced overall lipid levels and of bioactive lipid eicosanoids. Moreover, dietary supplementation of eicosanoid products of CYP-29A3 restores stress sensitivity of metl-5 mutant worms. Thus methylation of a specific residue of 18S rRNA by METL-5 selectively enhances translation of cyp-29A3, to increase production of eicosanoids that increase stress-related death.
2019-12-31 | GSE131269 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE26376: Microarray profiling of monocytic differentiaion reveals miRNA-mRNA intrinsic correlation (miRNA) GSE26377: Microarray profiling of monocytic differentiaion reveals miRNA-mRNA intrinsic correlation (gene expression) Refer to individual Series
2012-02-02 | E-GEOD-26379 | biostudies-arrayexpress
Project description:Gupta2009 - Eicosanoid Metabolism
Integrated model of eicosanoid metabolism and signaling based on lipidomics flux analysis.
This model is described in the article:
An integrated model of eicosanoid metabolism and signaling based on lipidomics flux analysis.
Gupta S, Maurya MR, Stephens DL, Dennis EA, Subramaniam S.
Biophys. J. 2009 Jun; 96(11):4542-51.
Abstract:
There is increasing evidence for a major and critical involvement of lipids in signal transduction and cellular trafficking, and this has motivated large-scale studies on lipid pathways. The Lipid Metabolites and Pathways Strategy consortium is actively investigating lipid metabolism in mammalian cells and has made available time-course data on various lipids in response to treatment with KDO(2)-lipid A (a lipopolysaccharide analog) of macrophage RAW 264.7 cells. The lipids known as eicosanoids play an important role in inflammation. We have reconstructed an integrated network of eicosanoid metabolism and signaling based on the KEGG pathway database and the literature and have developed a kinetic model. A matrix-based approach was used to estimate the rate constants from experimental data and these were further refined using generalized constrained nonlinear optimization. The resulting model fits the experimental data well for all species, and simulated enzyme activities were similar to their literature values. The quantitative model for eicosanoid metabolism that we have developed can be used to design experimental studies utilizing genetic and pharmacological perturbations to probe fluxes in lipid pathways.
This model is hosted on BioModels Database
and identified by: BIOMD0000000436
.
To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models
.
To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication
for more information.
2024-09-02 | BIOMD0000000436 | BioModels
Project description:we simultaneously deconstructed fibroblastic TRNW and reconstituted monocytic TRNW, and analyzed its monocytic and fibroblastic gene expression in comparison with that of fibroblastic TRNW deconstruction only or monocytic TRNW reconstitution only. This study provides an explicit example demonstrating how two networks together regulate gene expression during cell reprogramming processes.
2016-04-27 | GSE80676 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE27187: Expression profile of acute monocytic leukemia patients GSE27193: Normalization of whole-genome SNP data from acute monocytic leukemia patients for exome sequencing Refer to individual Series
2011-02-12 | E-GEOD-27244 | biostudies-arrayexpress