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dc.contributor.authorSommerfelt, Randi Magnus
dc.contributor.authorFeuerherm, Astrid Jullumstrø
dc.contributor.authorSkuland, Trine
dc.contributor.authorJohansen, Berit
dc.date.accessioned2015-04-20T19:19:00Z
dc.date.accessioned2015-06-08T09:05:50Z
dc.date.available2015-04-20T19:19:00Z
dc.date.available2015-06-08T09:05:50Z
dc.date.issued2015
dc.identifier.citationPLoS ONE 2015nb_NO
dc.identifier.issn1932-6203
dc.identifier.urihttp://hdl.handle.net/11250/284761
dc.description.abstractRheumatoid arthritis (RA) is an autoimmune disease characterized by chronic synovitis leading to destruction of cartilage and bone. PLA2 enzymes are key players in inflammation regulating the release of unsaturated fatty acids such as arachidonic acid (AA), a precursor of pro-inflammatory eicosanoids. Several lines of evidence point to toll-like receptors (TLRs) as drivers of synovitis and joint destruction in RA. However, few studies have addressed the implication of PLA2 activity downstream TLR activation in the synovium. Here, we aimed to characterize PLA2 enzyme involvement in TLR2-induced signaling in synovial fibroblast-like cells. TLRs1-7 and a range of sPLA2, iPLA2 and cPLA2 enzymes were found to be transcriptionally expressed in cultured synoviocytes. Activation of TLR2/1 and TLR2/6 led to phosphorylation of cPLA2α at Ser505, and induced AA release and PGE2 production; effects that were attenuated by cPLA2α inhibitors. In contrast, sPLA2 inhibitors did not affect AA or PGE2 release. cPLA2α inhibitors furthermore attenuated TLR-induced expression of IL-6, IL-8 and COX2. COX1/2 inhibitors attenuated TLR2/6-induced IL-6 transcription and protein production comparable to cPLA2α inhibition. Moreover, exogenously PGE2 added alone induced IL-6 production and completely rescued IL-6 transcription when added simultaneously with FSL-1 in the presence of a cPLA2α inhibitor. Our results demonstrate for the first time that cPLA2α is involved in TLR2/1- and TLR2/6-induced AA release, PGE2 production and pro-inflammatory cytokine expression in synoviocytes, possibly through COX/PGE2-dependent pathways. These findings expand our understanding of cPLA2α as a modulator of inflammatory molecular mechanisms in chronic diseases such as RA.nb_NO
dc.language.isoengnb_NO
dc.publisherPublic Library of Sciencenb_NO
dc.titleCytosolic phospholipase A2 modulates TLR2 signaling in synoviocytesnb_NO
dc.typeJournal articlenb_NO
dc.typePeer revieweden_GB
dc.date.updated2015-04-20T19:19:00Z
dc.source.journalPLoS ONEnb_NO
dc.identifier.doi10.1371/journal.pone.0119088
dc.identifier.cristin1132520
dc.description.localcodeCopyright: © 2015 Sommerfelt 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 credited.nb_NO


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