Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Genetics of gene expression across innate immune stimulation in primary monocytes

ABSTRACT: Gene expression arrays and genotyping data in primary human monocytes from healthy individuals of European ancestry that have either been unstimulated (naive) or exposed to IFN gamma (24h) or Lipopolysaccharide (2 or 24h duration).

ORGANISM(S): Homo sapiens

SUBMITTER: Seiko Makino

PROVIDER: E-MTAB-2232 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Distinct Transcriptional and Anti-Mycobacterial Profiles of Peripheral Blood Monocytes Dependent on the Ratio of Monocytes: Lymphocytes.

Naranbhai Vivek V Fletcher Helen A HA Tanner Rachel R O'Shea Matthew K MK McShane Helen H Fairfax Benjamin P BP Knight Julian C JC Hill Adrian V S AV

EBioMedicine 20151101 11

The ratio of monocytes and lymphocytes (ML ratio) in peripheral blood is associated with tuberculosis and malaria disease risk and cancer and cardiovascular disease outcomes. We studied anti-mycobacterial function and the transcriptome of monocytes in relation to the ML ratio. Mycobacterial growth inhibition assays of whole or sorted blood were performed and mycobacteria were enumerated by liquid culture. Transcriptomes of unstimulated CD14 + monocytes isolated by magnetic bead sorting were char ...[more]

PMID: 26870787

Publication: 1/3

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Project description:Background: Cardiovascular diseases remain the leading cause of morbidity and mortality worldwide, most of which are caused by atherosclerosis. Discerning processes that participate in macrophage-to-foam cell formation are critical for understanding the basic mechanisms underlying atherosclerosis. To explore the molecular mechanisms of foam cell formation, the differentially expressed proteins were identified. Methods: In this paper, human monocytes, macrophage colony-stimulating factor induced macrophages, and oxidized low-density lipoprotein induced foam cells were cultured, and tandem mass tag (TMT) labeling combined with mass spectrometry (MS) were performed to find associations between foam cell transformation and proteome profiles. Results: Totally, 5146 quantifiable proteins were identified, among which 1515 and 182 differentially expressed proteins (DEPs) were found in macrophage/monocyte and foam cell/macrophage, respectively, using a cutoff of 1.5-fold change. Subcellular localization analysis revealed that downregulated DEPs of macrophages/monocytes were mostly located in the nucleus and upregulated DEPs of foam cells/macrophages mostly located in the plasma membrane and extracellular. Functional analysis of DEPs demonstrated that cholesterol metabolism related proteins were upregulated in foam cells, whereas the immune response-related proteins were downregulated in foam cells. The protein-interaction network showed that the DEPs with the highest interaction intensity between macrophages and foam cells were mainly concentrated in lysosomes and the endoplasmic reticulum. Conclusions: This study for the first time to perform quantitative proteomic investigation by TMT labeling and LC-MS/MS to identify differentially expressed proteins in human monocyte, macrophage, and foam cell. The results confirmed cholesterol metabolism was upregulated in foam cells, while immune response was suppressed, which suggested that foam cells were not the population that promote inflammation. In addition, KEGG enrichment analysis and protein-protein interaction indicated that the differentially expressed proteins locating in the endoplasmic reticulum and lysosomes may be key targets to regulate foam cell formation. These data provide a basis for identifying the potential proteins associated with the molecular mechanism involved in the transformation of macrophages to foam cells.

Project description:Objective. Meningococcal sepsis remains an important cause of childhood morbidity and mortality. Largely due to logistic complexities of research in young children with acute life-threatening disease, very little is known regarding differential expression kinetics and molecular regulation of immune response genes in leukocyte subsets. Materials and methods. In this prospective case-control study, six children with meningococcal sepsis were included. Blood was drawn at four time points (t=0, t=8, t=24 and t=72 h after admission to the paediatric intensive care unit). Blood was also collected from matched controls. Detailed immunophenotyping of leukocytes was performed; RNA isolated from whole blood, lymphocytes, monocytes, and granulocytes was used to perform Affymetrix micro-array gene expression analysis. Results and conclusion. There were no differences in total leukocyte count between patients and controls. In contrast to previous in vitro studies we observed an unexpected decrease in NK cell numbers, as well as downregulation of NK cell specific and cytotoxic T-cell related gene expression in patients with meningococcal septic shock. By contrast, expression of genes, involved in innate immunity and several other pathways, differed between the different leukocyte subpopulations in a dynamic fashion. Compared to previously reported gene expression profiles, it was possible to define a meningococcal sepsis specific expression profile. Experiment Overall Design: In this prospective case-control study, six children with meningococcal sepsis were included. Blood was drawn at four time points (t=0, t=8, t=24 and t=72 h after admission to the paediatric intensive care unit). Blood was also collected from matched controls. Detailed immunophenotyping of leukocytes was performed; RNA isolated from whole blood, lymphocytes, monocytes, and granulocytes was used to perform Affymetrix micro-array gene expression analysis. Experiment Overall Design: No replicates were performed. Experiment Overall Design: Table 4. Results of between-subject analyses. Experiment Overall Design: Source Time (h) ca co/ca at t=T Experiment Overall Design: Blood t0: ca:2 3, co: a b c; t8: 2; t24 :ca:1 2 3; t72: ca:1 2. Experiment Overall Design: Lym t0: ca:2 3, co:a b c d;t8: ca:1 3 4;t24: ca:1 2 3 4 6; t72: ca: 1 2. Experiment Overall Design: Mono t0:ca: 1 3 4 6, co: a b d; t8: ca:1 2 3; t24:ca: 1 2 3; t72: ca:1. Experiment Overall Design: Numbers represent the patient identification numbers. Experiment Overall Design: Characters represent the individual controls.

Dataset Information

Genetics of gene expression across innate immune stimulation in primary monocytes

Publications

Distinct Transcriptional and Anti-Mycobacterial Profiles of Peripheral Blood Monocytes Dependent on the Ratio of Monocytes: Lymphocytes.

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