Identifying early inflammatory changes in monocyte derived macrophages from a population with IQ discrepant episodic memory

dc.contributor.authorDowner, Eric J.
dc.contributor.authorJones, Raasay S.
dc.contributor.authorMcDonald, Claire L.
dc.contributor.authorGreco, Eleonora
dc.contributor.authorBrennan, Sabina
dc.contributor.authorConnor, Thomas J.
dc.contributor.authorRobertson, Ian H.
dc.contributor.authorLynch, Marina A.
dc.contributor.funderScience Foundation Irelanden
dc.contributor.funderHealth Research Boarden
dc.contributor.funderAtlantic Philanthropiesen
dc.contributor.funderTrinity College Dublinen
dc.date.accessioned2016-02-17T11:46:18Z
dc.date.available2016-02-17T11:46:18Z
dc.date.issued2013
dc.description.abstractBackground: Cells of the innate immune system including monocytes and macrophages are the first line of defence against infections and are critical regulators of the inflammatory response. These cells express toll-like receptors (TLRs), innate immune receptors which govern tailored inflammatory gene expression patterns. Monocytes, which produce pro-inflammatory mediators, are readily recruited to the central nervous system (CNS) in neurodegenerative diseases. Methods: This study explored the expression of receptors (CD11b, TLR2 and TLR4) on circulating monocyte-derived macrophages (MDMs) and peripheral blood mononuclear cells (PBMCs) isolated from healthy elderly adults who we classified as either IQ memory-consistent (high-performing, HP) or IQ memory-discrepant (low-performing, LP). Results: The expression of CD11b, TLR4 and TLR2 was increased in MDMs from the LP group when compared to HP cohort. MDMs from both groups responded robustly to treatment with the TLR4 activator, lipopolysaccharide (LPS), in terms of cytokine production. Significantly, MDMs from the LP group displayed hypersensitivity to LPS exposure. Interpretation: Overall these findings define differential receptor expression and cytokine profiles that occur in MDMs derived from a cohort of IQ memory-discrepant individuals. These changes are indicative of inflammation and may be involved in the prodromal processes leading to the development of neurodegenerative disease.en
dc.description.sponsorshipScience Foundation Ireland (SFI Grant no.07/IN.1/B949); Health Research Board; Trinity College Dublin (Institute of Neuroscience Research Consortium on Neurodegeneration); Atlantic Philanthropies (Neuroenhancement for Independence in Elder Lives (NIEL))en
dc.description.statusPeer revieweden
dc.description.versionPublished Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.articleide63194
dc.identifier.citationDowner EJ, Jones RS, McDonald CL, Greco E, Brennan S, Connor TJ, et al. (2013) Identifying Early Inflammatory Changes in Monocyte-Derived Macrophages from a Population with IQ-Discrepant Episodic Memory. PLoS ONE 8(5): e63194. doi:10.1371/journal.pone.0063194en
dc.identifier.doi10.1371/journal.pone.0063194
dc.identifier.issn1932-6203
dc.identifier.issued5en
dc.identifier.journaltitlePLOS ONEen
dc.identifier.urihttps://hdl.handle.net/10468/2380
dc.identifier.volume8en
dc.language.isoenen
dc.publisherPublic Library of Scienceen
dc.rights@ 2013 Downer et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are crediteden
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectCentral nervous systemen
dc.subjectMild cognitive impairmenten
dc.subjectBlood mononuclear cellsen
dc.subjectAmyloid beta proteinen
dc.subjectAlzheimers diseaseen
dc.subjectImmune systemen
dc.subjectMicroglial activationen
dc.subjectSignal transductionen
dc.subjectCytokine productionen
dc.subjectDendritic cellsen
dc.titleIdentifying early inflammatory changes in monocyte derived macrophages from a population with IQ discrepant episodic memoryen
dc.typeArticle (peer-reviewed)en
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