Identification of 34 novel proinflammatory proteins in a genome-wide macrophage functional screen

Signal transduction pathways activated by Toll-like Receptors and the IL-1 family of cytokines are fundamental to mounting an innate immune response and thus to clearing pathogens and promoting wound healing. Whilst mechanistic understanding of the regulation of innate signalling pathways has advanc...

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Veröffentlicht in:PloS one 2012-07, Vol.7 (7), p.e42388-e42388
Hauptverfasser: Wyllie, David H, Søgaard, Karen C, Holland, Karen, Yaobo, Xu, Bregu, Migena, Hill, Adrian V S, Kiss-Toth, Endre
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container_end_page e42388
container_issue 7
container_start_page e42388
container_title PloS one
container_volume 7
creator Wyllie, David H
Søgaard, Karen C
Holland, Karen
Yaobo, Xu
Bregu, Migena
Hill, Adrian V S
Kiss-Toth, Endre
description Signal transduction pathways activated by Toll-like Receptors and the IL-1 family of cytokines are fundamental to mounting an innate immune response and thus to clearing pathogens and promoting wound healing. Whilst mechanistic understanding of the regulation of innate signalling pathways has advanced considerably in recent years, there are still a number of critical controllers to be discovered. In order to characterise novel regulators of macrophage inflammation, we have carried out an extensive, cDNA-based forward genetic screen and identified 34 novel activators, based on their ability to induce the expression of cxcl2. Many are physiologically expressed in macrophages, although the majority of genes uncovered in our screen have not previously been linked to innate immunity. We show that expression of particular activators has profound but distinct impacts on LPS-induced inflammatory gene expression, including switch-type, amplifier and sensitiser behaviours. Furthermore, the novel genes identified here interact with the canonical inflammatory signalling network via specific mechanisms, as demonstrated by the use of dominant negative forms of IL1/TLR signalling mediators.
doi_str_mv 10.1371/journal.pone.0042388
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subjects Animals
Biology
Cell Line
Cellular signal transduction
Clearing
Cloning
Cytokines
Deoxyribonucleic acid
DNA
Gene expression
Genes
Genetic screening
Genetic testing
Genome
Genomes
Genomics
Identification
Immune response
Immune system
Immunity
Inflammation
Inflammation - metabolism
Inflammation - physiopathology
Innate immunity
Interleukin 1
Kinases
Library collections
Lipopolysaccharides
Macrophages
Macrophages - physiology
Medicine
Mice
Potassium
Proteins
Receptors
Regulators
Rodents
Signal processing
Signal Transduction
Signaling
Toll-like receptors
Variance analysis
Wound healing
title Identification of 34 novel proinflammatory proteins in a genome-wide macrophage functional screen
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