dc.contributor.author | Nilsen, Nadra | |
dc.contributor.author | Gregory I., Vladimer | |
dc.contributor.author | Stenvik, Jørgen | |
dc.contributor.author | Ørning, Mathias Pontus | |
dc.contributor.author | Zeid-Kilani, Maria Vanessa | |
dc.contributor.author | Bugge, Marit | |
dc.contributor.author | Bergstrøm, Bjarte | |
dc.contributor.author | Conlon, Joseph | |
dc.contributor.author | Husebye, Harald | |
dc.contributor.author | Amy, Hise | |
dc.contributor.author | Fitzgerald, Katherine A. | |
dc.contributor.author | Espevik, Terje | |
dc.contributor.author | Lien, Egil | |
dc.date.accessioned | 2017-10-04T12:23:38Z | |
dc.date.available | 2017-10-04T12:23:38Z | |
dc.date.created | 2015-01-08T09:37:54Z | |
dc.date.issued | 2015 | |
dc.identifier.citation | Journal of Biological Chemistry. 2015, 290 (6), 3209-3222. | nb_NO |
dc.identifier.issn | 0021-9258 | |
dc.identifier.uri | http://hdl.handle.net/11250/2458403 | |
dc.description.abstract | Toll-like receptors (TLRs) are involved in sensing invading microbes by host innate immunity. TLR2 recognizes bacterial lipoproteins/lipopeptides, and lipopolysaccharide activates TLR4. TLR2 and TLR4 signal via the Toll/interleukin-1 receptor adaptors MyD88 and MAL, leading to NF-κB activation. TLR4 also utilizes the adaptors TRAM and TRIF, resulting in activation of interferon regulatory factor (IRF) 3. Here, we report a new role for TRAM and TRIF in TLR2 regulation and signaling. Interestingly, we observed that TLR2-mediated induction of the chemokine Ccl5 was impaired in TRAM or TRIF deficient macrophages. Inhibition of endocytosis reduced Ccl5 release, and the data also suggested that TRAM and TLR2 co-localize in early endosomes, supporting the hypothesis that signaling may occur from an intracellular compartment. Ccl5 release following lipoprotein challenge additionally involved the kinase Tbk-1 and Irf3, as well as MyD88 and Irf1. Induction of Interferon-β and Ccl4 by lipoproteins was also partially impaired in cells lacking TRIF cells. Our results show a novel function of TRAM and TRIF in TLR2-mediated signal transduction, and the findings broaden our understanding of how Toll/interleukin-1 receptor adaptor proteins may participate in signaling downstream from TLR2. | nb_NO |
dc.language.iso | eng | nb_NO |
dc.publisher | American Society for Biochemistry and Molecular Biology | nb_NO |
dc.title | A role for the adaptor proteins TRAM and TRIF in toll-like receptor 2 signaling | nb_NO |
dc.type | Journal article | nb_NO |
dc.type | Peer reviewed | nb_NO |
dc.description.version | publishedVersion | nb_NO |
dc.source.pagenumber | 3209-3222 | nb_NO |
dc.source.volume | 290 | nb_NO |
dc.source.journal | Journal of Biological Chemistry | nb_NO |
dc.source.issue | 6 | nb_NO |
dc.identifier.doi | 10.1074/jbc.M114.593426 | |
dc.identifier.cristin | 1192916 | |
dc.relation.project | Lovisenberg diakonale høgskole: Kreftfondet HMN | nb_NO |
dc.relation.project | Norges forskningsråd: 223255 | nb_NO |
dc.description.localcode | This research was originally published in Journal of Biological Chemistry, December 11, 2014 by The American Society for Biochemistry and Molecular Biology, Inc. | nb_NO |
cristin.unitcode | 194,65,15,0 | |
cristin.unitname | Institutt for kreftforskning og molekylær medisin | |
cristin.ispublished | true | |
cristin.fulltext | original | |
cristin.fulltext | preprint | |
cristin.qualitycode | 2 | |