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dc.contributor.authorLau, Corinna
dc.contributor.authorNygård, Ståle
dc.contributor.authorFure, Hilde
dc.contributor.authorOlstad, Ole Kristoffer
dc.contributor.authorHolden, Marit
dc.contributor.authorLappegård, Knut Tore
dc.contributor.authorBrekke, Ole Lars
dc.contributor.authorEspevik, Terje
dc.contributor.authorHovig, Johannes Eivind
dc.contributor.authorMollnes, Tom Eirik
dc.date.accessioned2016-02-11T07:32:32Z
dc.date.available2016-02-11T07:32:32Z
dc.date.issued2015-02-23
dc.description.abstractSystemic inflammation like in sepsis is still lacking specific diagnostic markers and effective therapeutics. The first line of defense against intruding pathogens and endogenous damage signals is pattern recognition by e.g., complement and Toll-like receptors (TLR). Combined inhibition of a key complement component (C3 and C5) and TLR-co-receptor CD14 has been shown to attenuate certain systemic inflammatory responses. Using DNA microarray and gene annotation analyses, we aimed to decipher the effect of combined inhibition of C3 and CD14 on the transcriptional response to bacterial challenge in human whole blood. Importantly, combined inhibition reversed the transcriptional changes of 70% of the 2335 genes which significantly responded to heat-inactivated Escherichia coli by on average 80%. Single inhibition was less efficient (p<0.001) but revealed a suppressive effect of C3 on 21% of the responding genes which was partially counteracted by CD14. Furthermore, CD14 dependency of the Escherichia coli-induced response was increased in C5-deficient compared to C5-sufficient blood. The observed crucial distinct and synergistic roles for complement and CD14 on the transcriptional level correspond to their broad impact on the inflammatory response in human blood, and their combined inhibition may become inevitable in the early treatment of acute systemic inflammation.en_US
dc.identifier.citationPLoS ONE 10(2015) nr. 2 s. -en_US
dc.identifier.cristinIDFRIDAID 1251673
dc.identifier.doi10.1371/journal.pone.0117261
dc.identifier.issn1932-6203
dc.identifier.urihttps://hdl.handle.net/10037/8459
dc.identifier.urnURN:NBN:no-uit_munin_8031
dc.language.isoengen_US
dc.publisherPublic Library of Science (PLoS)en_US
dc.rights.accessRightsopenAccess
dc.subjectVDP::Medisinske Fag: 700::Klinisk medisinske fag: 750en_US
dc.subjectVDP::Medical disciplines: 700::Clinical medical disciplines: 750en_US
dc.titleCD14 and complement crosstalk and largely mediate the transcriptional response to Escherichia coli in human whole blood as revealed by DNA microarrayen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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