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dc.contributor.authorIslam, Rakibul
dc.contributor.authorIslam, Mohammad Mirazul
dc.contributor.authorNilsson, Per H.
dc.contributor.authorMohlin, Camilla
dc.contributor.authorHagen, Kjersti Thorvaldsen
dc.contributor.authorPaschalis, Eleftherios I.
dc.contributor.authorWoods, Russell L.
dc.contributor.authorBhowmick, Sabuj Chandra
dc.contributor.authorDohlman, Claes H.
dc.contributor.authorEspevik, Terje
dc.contributor.authorChodosh, James
dc.contributor.authorGonzalez-Andrades, Miguel
dc.contributor.authorMollnes, Tom Eirik
dc.date.accessioned2021-09-13T07:11:20Z
dc.date.available2021-09-13T07:11:20Z
dc.date.issued2021-03-27
dc.description.abstractInadequate supplies of donor corneas have evoked an escalating interest in corneal xenotransplantation. However, innate immune responses contribute significantly to the mechanism of xenograft rejection. We hypothesized that complement component C5 and TLR co-receptor CD14 inhibition would inhibit porcine cornea induced innate immune responses. Therefore, we measured cytokine release in human blood, induced by three forms of corneal xenografts with or without inhibitors. Native porcine cornea (NPC) induced interleukins (IL-1β, IL-2, IL-6, IL-8, IL-1ra), chemokines (MCP-1, MIP-1α, MIP-1β) and other cytokines (TNF, G-CSF, INF-γ, FGF-basic). Decellularized (DPC) and gamma-irradiated cornea (g-DPC) elevated the release of those cytokines. C5-blockade by eculizumab inhibited all the cytokines except G-CSF when induced by NPC. However, C5-blockade failed to reduce DPC and g-DPC induced cytokines. Blockade of CD14 inhibited DPC-induced cytokines except for IL-8, MCP-1, MIP-1α, and G-CSF, while it inhibited all of them when induced by g-DPC. Combined blockade of C5 and CD14 inhibited the maximum number of cytokines regardless of the xenograft type. Finally, by using the TLR4 specific inhibitor Eritoran, we showed that TLR4 activation was the basis for the CD14 effect. Thus, blockade of C5, when combined with TLR4 inhibition, may have therapeutic potential in pig-to-human corneal xenotransplantation.en_US
dc.identifier.citationIslam, Islam, Nilsson, Mohlin, Hagen, Paschalis, Woods, Bhowmick, Dohlman, Espevik, Chodosh, Gonzalez-Andrades, Mollnes. Combined blockade of complement C5 and TLR co-receptor CD14 synergistically inhibits pig-to-human corneal xenograft induced innate inflammatory responses. Acta Biomaterialia. 2021;127:169-179en_US
dc.identifier.cristinIDFRIDAID 1916732
dc.identifier.doi10.1016/j.actbio.2021.03.047
dc.identifier.issn1742-7061
dc.identifier.issn1878-7568
dc.identifier.urihttps://hdl.handle.net/10037/22491
dc.language.isoengen_US
dc.publisherElsevieren_US
dc.relation.journalActa Biomaterialia
dc.relation.projectIDHelse Sør-Øst RHF: 2016101en_US
dc.rights.accessRightsopenAccessen_US
dc.rights.holderCopyright 2021 The Author(s)en_US
dc.subjectVDP::Medical disciplines: 700::Basic medical, dental and veterinary science disciplines: 710en_US
dc.subjectVDP::Medisinske Fag: 700::Basale medisinske, odontologiske og veterinærmedisinske fag: 710en_US
dc.titleCombined blockade of complement C5 and TLR co-receptor CD14 synergistically inhibits pig-to-human corneal xenograft induced innate inflammatory responsesen_US
dc.type.versionpublishedVersionen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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