Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcription profiling of human macrophages from ulcerative colitis patients or healthy control individuals, either unstimulated or stimulated with heat killed E. coli

ABSTRACT: Comparison of gene expression in macrophages from ulcerative colitis patients or healthy control individuals, either unstimulated or stimulated with heat killed E. coli

INSTRUMENT(S): 418 [Affymetrix]

ORGANISM(S): Homo sapiens

SUBMITTER: Ann Walker

PROVIDER: E-TABM-734 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Disordered macrophage cytokine secretion underlies impaired acute inflammation and bacterial clearance in Crohn's disease.

Smith Andrew M AM Rahman Farooq Z FZ Hayee Bu'Hussain B Graham Simon J SJ Marks Daniel J B DJ Sewell Gavin W GW Palmer Christine D CD Wilde Jonathan J Foxwell Brian M J BM Gloger Israel S IS Sweeting Trevor T Marsh Mark M Walker Ann P AP Bloom Stuart L SL Segal Anthony W AW

The Journal of experimental medicine 20090803 9

The cause of Crohn's disease (CD) remains poorly understood. Counterintuitively, these patients possess an impaired acute inflammatory response, which could result in delayed clearance of bacteria penetrating the lining of the bowel and predispose to granuloma formation and chronicity. We tested this hypothesis in human subjects by monitoring responses to killed Escherichia coli injected subcutaneously into the forearm. Accumulation of (111)In-labeled neutrophils at these sites and clearance of ...[more]

PMID: 19652016

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Project description:In vertebrates, all cells except circulating blood cells must adhere to support their normal growth and functions. The adherence to extracellular matrix and/or other cells is critical and adherent cells placed in non-adherent conditions either die or form multicellular spheroids. Placing cells in non-adherent conditions has been used to induce differentiation in teratocarcinoma cells and more recently to form organoids . Because of such important consequences induced by cell adhesion on cell growth and function, the transition between adherent and non-adherent states is rather rare. There are however physiological situations, such as blood cells diapedesis, during which cells that circulate into the blood stream must adhere to the endothelial cells and cross the endothelial barrier to reach target tissues. Another example of transition, from an adherent to a non-adherent state, is observed in the metastasic process, where cells detach from the tumor mass and circulate in the blood and lymphatic vasculature prior to reattaching and extravasating to colonize distant organs. The comparative analysis of the only effects of adherence on cellular functions is complicated by the fact that in many study models the acquisition or loss of adherence induces major alterations in cell physiology that would obscure the effects of the adherence itself. For example, P19 teratocarcinoma cells differentiate in suspension spheroids while they do not in adhering conditions. In this context, the comparison between spheroids and adherent cells would not be a comparison between adherent and non-adherent cells, but between differentiated cells adhering between them and undifferentiated cells adhering on plastic. Mouse macrophage cell lines represent one of the rare experimental models that may be suitable to compare the adherent and non-adherent states. Indeed, they grow equally well under adherent and non-adherent conditions and keep their differentiated functions under both conditions. We therefore decided to use this model to analyze the changes between the adherent and the non-adherent state using a broad approach, based on proteomics.

Project description:Macrophages provide an interface between innate and adaptive immunity and are important long-lived reservoirs for Human Immunodeficiency Virus Type-1 (HIV-1). Multiple genetic networks involved in regulating signal transduction cascades and immune responses in macrophages are coordinately modulated by HIV-1 infection. To evaluate complex interrelated processes and to assemble an integrated view of activated signaling networks, a systems biology strategy was applied to genomic and proteomic responses by primary human macrophages over the course of HIV-1 infection. Macrophage responses, including cell cycle, calcium, apoptosis, mitogen-activated protein kinases (MAPK), and cytokines/chemokines, to HIV-1 were temporally regulated, in the absence of cell proliferation. In contrast, Toll-like receptor (TLR) pathways remained unaltered by HIV-1, although TLRs 3, 4, 7, and 8 were expressed and responded to ligand stimulation in macrophages. HIV-1 failed to activate phosphorylation of IRAK-1 or IRF-3, modulate intracellular protein levels of Mx1, an interferon-stimulated gene, or stimulate secretion of TNF, IL-1b, or IL-6. Activation of pathways other than TLR was inadequate to stimulate, via cross-talk mechanisms through molecular hubs, the production of proinflammatory cytokines typical of a TLR response. HIV-1 sensitized macrophage responses to TLR ligands, and the magnitude of viral priming was related to virus replication. HIV-1 induced a primed, proinflammatory state, M1HIV, which increased the responsiveness of macrophages to TLR ligands. HIV-1 might passively evade pattern recognition, actively inhibit or suppress recognition and signaling, or require dynamic interactions between macrophages and other cells, such as lymphocytes or endothelial cells. HIV-1 evasion of TLR recognition and simultaneous priming of macrophages may represent a strategy for viral survival, contribute to immune pathogenesis, and provide important targets for therapeutic approaches. Affymetrix arrays were used to identify genomic macrophage response to HIV during viral spread in culture. Experiment Overall Design: An HIV-1 spreading infection was established in primary human macrophages. RNA was extracted from both viral- and mock-infected macrophages cultures over 7 days and hybridized to Affymetrix HG-U95Av2 GeneChips for analysis.

Dataset Information

Transcription profiling of human macrophages from ulcerative colitis patients or healthy control individuals, either unstimulated or stimulated with heat killed E. coli

Publications

Disordered macrophage cytokine secretion underlies impaired acute inflammation and bacterial clearance in Crohn's disease.

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