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Genomic analysis of LPS-stimulated myeloid cells identifies a common pro-inflammatory response but divergent IL-10 anti-inflammatory responses

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dc.contributor.authorHutchins, Andrew Paul
dc.contributor.authorTakahashi, Yoshiko
dc.contributor.authorMiranda Saavedra, Diego
dc.contributor.funderJapan Society for the Promotion of Science
dc.contributor.funderNational Natural Science Foundation of China
dc.contributor.funderChina Postdoctoral Science Foundation
dc.contributor.rorhttps://ror.org/02jjdwm75
dc.date.accessioned2024-07-08T13:14:56Z
dc.date.accessioned2024-09-16T11:20:28Z
dc.date.available2024-07-08T13:14:56Z
dc.date.available2024-09-16T11:20:28Z
dc.date.issued2015
dc.description.abstractInflammation is an essential physiological response to infection and injury that must be kept within strict bounds. The IL-10/STAT3 anti-inflammatory response (AIR) is indispensable for controlling the extent of inflammation,although the complete mechanisms downstream of STAT3 have not yet been elucidated. The AIR is widely known to extend to other myeloid cells,but it has best been characterized in macrophages. Here we set out to characterize the LPS-mediated pro-inflammatory response and the AIR across a range of myeloid cells. We found that whereas the LPS-induced pro-inflammatory response is broadly similar among macrophages,dendritic cells,neutrophils,mast cells and eosinophils,the AIR is drastically different across all myeloid cell types that respond to IL-10 (all bar eosinophils). We propose a model whereby the IL-10/STAT3 AIR works by selectively inhibiting specific pathways in distinct cell types: in macrophages the AIR most likely works through the inhibition of NF-?B target genes; in DCs and mast cells through indirect IRF disruption; and in neutrophils through IRF disruption and possibly also indirect NF-?B inhibition. In summary,no conserved IL-10/STAT3 AIR effectors were identified; instead a cell type-specific model of the AIR is proposed. © 2015,Nature Publishing Group. All rights reserved.
dc.description.fundingtypeWe thank Professor Paul Crocker, Dr. Hannah Richards and Dr. Szandor Simmons for technical advice and Ms. Mineko Tanimoto for secretarial support. D.M.-S. acknowledges financial support from the Japan Society for the Promotion of Science (JSPS) through the WPI-IFReC Research Program. A.P.H. is funded by the National Natural Science Foundation of China (31471242) and the China Postdoctoral Science Foundation (2014M552250).
dc.formatapplication/pdf
dc.identifier.citationHutchins, A. P., Takahashi, Y., & Miranda-Saavedra, D. (2015). Genomic analysis of LPS-stimulated myeloid cells identifies a common pro-inflammatory response but divergent IL-10 anti-inflammatory responses. Scientific reports, 5(1), 9100.
dc.identifier.doihttps://doi.org/10.1038/srep09100
dc.identifier.issn20452322
dc.identifier.officialurlhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-84924777822&doi=10.1038%2fsrep09100&partnerID=40&md5=f5a202f684cfe4b4996c8dfe46a26c1f
dc.identifier.urihttps://hdl.handle.net/20.500.14417/3268
dc.journal.titleScientific Reports
dc.language.isoeng
dc.page.total0
dc.publisherNature Publishing Group
dc.relation.entityIE University
dc.relation.projectIDNSFC: 31471242
dc.relation.projectID2014M552250
dc.rightsAttribution 4,0 International
dc.rights.accessRightsinfo:eu-repo/semantics/openAccess
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subject.otherautacoid
dc.subject.othercytokine
dc.subject.otherinterleukin 10
dc.subject.otherlipopolysaccharide
dc.subject.otherSTAT3 protein
dc.subject.otherantibody specificity
dc.subject.otherbone marrow cell
dc.subject.othercluster analysis
dc.subject.othergene expression profiling
dc.subject.othergene expression regulation
dc.subject.othergenetics
dc.subject.othergenomics
dc.subject.otherhuman
dc.subject.otherimmunology
dc.subject.otherinflammation
dc.subject.otherleukocyte
dc.subject.othermacrophage
dc.subject.othermetabolism
dc.subject.otherCluster Analysis
dc.subject.otherCytokines
dc.subject.otherGene Expression Profiling
dc.subject.otherGene Expression Regulation
dc.subject.otherGenomics
dc.subject.otherHumans
dc.subject.otherInflammation
dc.subject.otherInflammation Mediators
dc.subject.otherInterleukin-10
dc.subject.otherLeukocytes
dc.subject.otherLipopolysaccharides
dc.subject.otherMacrophages
dc.subject.otherMyeloid Cells
dc.subject.otherOrgan Specificity
dc.subject.otherSTAT3 Transcription Factor
dc.titleGenomic analysis of LPS-stimulated myeloid cells identifies a common pro-inflammatory response but divergent IL-10 anti-inflammatory responses
dc.typeinfo:eu-repo/semantics/article
dc.version.typeinfo:eu-repo/semantics/publishedVersion
dc.volume.number5
dspace.entity.typePublication
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