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dc.contributor.authorFasler-Kan, Elizavetaen_US
dc.contributor.authorBarteneva, Natasha Sen_US
dc.contributor.authorKetterer, Sylviaen_US
dc.contributor.authorWunderlich, Kerstinen_US
dc.contributor.authorReschner, Ancaen_US
dc.contributor.authorNurzhanova, Asilen_US
dc.contributor.authorFlammer, Josefen_US
dc.contributor.authorHuwyler, Jörgen_US
dc.contributor.authorMeyer, Peteren_US
dc.date.accessioned2015-01-05T18:28:27Z
dc.date.issued2013en_US
dc.identifier.citationFasler-Kan, Elizaveta, Natasha S Barteneva, Sylvia Ketterer, Kerstin Wunderlich, Anca Reschner, Asil Nurzhanova, Josef Flammer, Jörg Huwyler, and Peter Meyer. 2013. “Human cytokines activate JAK–STAT signaling pathway in porcine ocular tissue.” Xenotransplantation 20 (6): 469-480. doi:10.1111/xen.12070. http://dx.doi.org/10.1111/xen.12070.en
dc.identifier.issn0908-665Xen
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:13581256
dc.description.abstractBackground: The JAK/STAT (Janus Tyrosine Kinase, Signal Transducers and Activators of Transcription) pathway is associated with cytokine or growth factor receptors and it is critical for growth control, developmental regulation and homeostasis. The use of porcine ocular cells as putative xenotransplants appears theoretically possible. The aim of this study was to investigate the response of various porcine ocular cells in vitro to human cytokines in regard to the activation of JAK-STAT signaling pathways. Methods: Porcine lens epithelial cells, pigmented iris epithelial cells and pigmented ciliary body cells were used in this study. These cells were isolated from freshly enucleated porcine eyes by enzymatic digestion. Cultured cells between passages 3–8 were used in all experiments. Electromobility shift assay (EMSA), proliferation assay, immunofluorescence staining and flow cytometry were used to evaluate the JAK-STAT signaling pathway in these cells. Results: JAK/STAT signaling pathways could be activated in porcine pigmented epithelial ciliary body cells, in pigmented iris epithelial cells and in lens epithelial cells in response to porcine and human interferons and cytokines. All cells showed very strong STAT1 activation upon stimulation with porcine interferon-gamma. Porcine ocular cells also respond to human cytokines; IFN-alpha induced strong activation of STAT1 in EMSA, flow cytometry and immunofluorescence experiments whereas activation of STAT3 was less strong in EMSA, but strong in flow cytometry and immunofluorescence. Human recombinant IL-6 activated STAT3 and human IL-4 activated STAT6. With the help of immunofluorescence assay and flow cytometry we observed nuclear localization of STAT proteins after activation of porcine ocular cells with cytokines and interferons. Human IFN-α had an inhibitory effect on porcine ocular cells in proliferation assays. Conclusion: Our study demonstrated that some types of human cytokines and interferon activate intracellular JAK-STAT signaling pathways in porcine ocular cells. We hypothesize that direct stimulation of the JAK-STAT pathway in porcine cells in response to human cytokines will lead to complications or failure, if pig-to-human ocular tissue xenotransplantation were to be carried out. For successful xenotransplantation among other obstacles there must be new approaches developed to regulate signaling pathways.en
dc.language.isoen_USen
dc.publisherBlackWell Publishing Ltden
dc.relation.isversionofdoi:10.1111/xen.12070en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC4235432/pdf/en
dash.licenseLAAen_US
dc.subjectcytokine signalingen
dc.subjectinterferonen
dc.subjectpig retinaen
dc.subjectSTAT proteinsen
dc.subjectxenotransplantationen
dc.titleHuman cytokines activate JAK–STAT signaling pathway in porcine ocular tissueen
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalXenotransplantationen
dc.date.available2015-01-05T18:28:27Z
dc.identifier.doi10.1111/xen.12070*


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