dc.date.accessioned | 2021-09-07T15:52:16Z | |
dc.date.available | 2021-09-07T15:52:16Z | |
dc.date.created | 2021-06-18T12:06:10Z | |
dc.date.issued | 2021 | |
dc.identifier.citation | Islam, Rakibul Islam, Mohammad Mirazul Nilsson, Per H. Mohlin, Camilla Hagen, Kjersti Thorvaldsen Paschalis, Eleftherios I. Woods, Russell L. Bhowmick, Sabuj Chandra Dohlman, Claes H. Espevik, Terje Chodosh, James Gonzalez-Andrades, Miguel Mollnes, Tom Eirik . 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, 169-179 | |
dc.identifier.uri | http://hdl.handle.net/10852/87696 | |
dc.description.abstract | Inadequate 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. | |
dc.language | EN | |
dc.rights | Attribution 4.0 International | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | |
dc.title | Combined blockade of complement C5 and TLR co-receptor CD14 synergistically inhibits pig-to-human corneal xenograft induced innate inflammatory responses | |
dc.type | Journal article | |
dc.creator.author | Islam, Rakibul | |
dc.creator.author | Islam, Mohammad Mirazul | |
dc.creator.author | Nilsson, Per H. | |
dc.creator.author | Mohlin, Camilla | |
dc.creator.author | Hagen, Kjersti Thorvaldsen | |
dc.creator.author | Paschalis, Eleftherios I. | |
dc.creator.author | Woods, Russell L. | |
dc.creator.author | Bhowmick, Sabuj Chandra | |
dc.creator.author | Dohlman, Claes H. | |
dc.creator.author | Espevik, Terje | |
dc.creator.author | Chodosh, James | |
dc.creator.author | Gonzalez-Andrades, Miguel | |
dc.creator.author | Mollnes, Tom Eirik | |
cristin.unitcode | 185,53,18,12 | |
cristin.unitname | Immunologi og transfusjonsmedisin | |
cristin.ispublished | true | |
cristin.fulltext | original | |
cristin.qualitycode | 1 | |
dc.identifier.cristin | 1916732 | |
dc.identifier.bibliographiccitation | info:ofi/fmt:kev:mtx:ctx&ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Acta Biomaterialia&rft.volume=127&rft.spage=169&rft.date=2021 | |
dc.identifier.jtitle | Acta Biomaterialia | |
dc.identifier.volume | 127 | |
dc.identifier.startpage | 169 | |
dc.identifier.endpage | 179 | |
dc.identifier.doi | https://doi.org/10.1016/j.actbio.2021.03.047 | |
dc.identifier.urn | URN:NBN:no-90327 | |
dc.type.document | Tidsskriftartikkel | |
dc.type.peerreviewed | Peer reviewed | |
dc.source.issn | 1742-7061 | |
dc.identifier.fulltext | Fulltext https://www.duo.uio.no/bitstream/handle/10852/87696/2/Postnr%2B1916732_Islam%2Bet%2Bal_Acta%2BBiomat_1-s2.0-S1742706121001975-main.pdf | |
dc.type.version | PublishedVersion | |
dc.relation.project | HSØ/2016101 | |