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dc.contributor.authorIliev, Dimitar Borisov
dc.contributor.authorStrandskog, Guro
dc.contributor.authorNepal, Arpita
dc.contributor.authorAspar, Augusta
dc.contributor.authorOlsen, Randi
dc.contributor.authorJørgensen, Jorunn B
dc.contributor.authorWolfson, Deanna
dc.contributor.authorAhluwalia, Balpreet Singh
dc.contributor.authorHandzhiyski, Jordan
dc.contributor.authorMironova, Roumyana
dc.date.accessioned2018-11-07T09:21:31Z
dc.date.available2018-11-07T09:21:31Z
dc.date.issued2018-06-28
dc.description.abstractExosomes are distinguished from other types of extracellular vesicles by their small and relatively uniform size (30-100 nm) and their composition which reflects their endo-lysosomal origin. Involvement of these extracellular organelles in intercellular communication and their implication in pathological conditions has fuelled intensive research on mammalian exosomes; however, currently, very little is known about exosomes in lower vertebrates. Here we show that, in primary cultures of head kidney leukocytes from Atlantic salmon (<i>Salmo salar</i>), phosphorothioate CpG oligodeoxynucleotides induce secretion of vesicles with characteristics very similar to these of mammalian exosomes. Further experiments revealed that the oligonucleotide-induced exosome secretion did not depend on the CpG motifs but it relied on the phosphorothioate modification of the internucleotide linkage. Exosome secretion was also induced by genomic bacterial and eukaryotic DNA in toll-like receptor 9-negative piscine and human cell lines demonstrating that this is a phylogenetically conserved phenomenon which does not depend on activation of immune signaling pathways. In addition to exosomes, stimulation with phosphorothioate oligonucleotides and genomic DNA induced secretion of LC3B-II, an autophagosome marker, which was associated with vesicles of diverse size and morphology, possibly derived from autophagosome-related intracellular compartments. Overall, this work reveals a previously unrecognized biological activity of phosphorothioate ODNs and genomic DNA – their capacity to induce secretion of exosomes and other types of extracellular vesicles. This finding might help shed light on the side effects of therapeutic phosphorothioate oligodeoxynucleotides and the biological activity of extracellular genomic DNA which is often upregulated in pathological conditions.en_US
dc.description.sponsorshipEEA UiT The Arctic University of Norwayen_US
dc.descriptionThis is the submitted manuscript version of the following article Iliev, D., Strandskog, G., Nepal, A., Aspar, A., Olsen, R., Jørgensen, J., ... Mironova, R. (2018). Stimulation of exosome release by extracellular DNA is conserved across multiple cell types. <i>The FEBS Journal</i>, 285(16), 3114-3133. https://doi.org/10.1111/febs.14601. Published version available at <a href=https://doi.org/10.1111/febs.14601> https://doi.org/10.1111/febs.14601</a>.en_US
dc.identifier.citationIliev, D., Strandskog, G., Nepal, A., Aspar, A., Olsen, R., Jørgensen, J., ... Mironova, R. (2018). Stimulation of exosome release by extracellular DNA is conserved across multiple cell types. <i>The FEBS Journal</i>, 285(16), 3114-3133. <a href=https://doi.org/10.1111/febs.14601> https://doi.org/10.1111/febs.14601</a>en_US
dc.identifier.cristinIDFRIDAID 1627639
dc.identifier.doi10.1111/febs.14601
dc.identifier.issn1742-464X
dc.identifier.issn1742-4658
dc.identifier.urihttps://hdl.handle.net/10037/14111
dc.language.isoengen_US
dc.publisherWileyen_US
dc.relation.journalThe FEBS Journal
dc.relation.projectIDinfo:eu-repo/grantAgreement/RCN/FRIMEDBIO/230735/Norway/Exosomes from salmon (Salmo salar) leukocytes - composition, functions, biogenesis and immunodiagnostic potential//en_US
dc.rights.accessRightsopenAccessen_US
dc.subjectVDP::Agriculture and fishery disciplines: 900::Fisheries science: 920en_US
dc.subjectVDP::Landbruks- og Fiskerifag: 900::Fiskerifag: 920en_US
dc.subjectexosomesen_US
dc.subjectextracellular DNAen_US
dc.subjectextracellular vesiclesen_US
dc.subjectmicrovesiclesen_US
dc.subjectphosphorothioate oligodeoxynucleotidesen_US
dc.subjectsalmon leukocytesen_US
dc.titleStimulation of exosome release by extracellular DNA is conserved across multiple cell typesen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typeManuskriptno
dc.typePeer revieweden_US
dc.typePreprinten_US


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