{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T19:03:33Z","timestamp":1762542213130},"reference-count":69,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2013,11,1]],"date-time":"2013-11-01T00:00:00Z","timestamp":1383264000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Xenotransplantation"],"published-print":{"date-parts":[[2013,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>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\u2010STAT signaling pathways.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>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\u20138 were used in all experiments. Electromobility shift assay (<jats:styled-content style=\"fixed-case\">EMSA<\/jats:styled-content>), proliferation assay, immunofluorescence staining and flow cytometry were used to evaluate the JAK\u2010STAT signaling pathway in these cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>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\u2010gamma. Porcine ocular cells also respond to human cytokines; IFN\u2010alpha induced strong activation of STAT1 in <jats:styled-content style=\"fixed-case\">EMSA<\/jats:styled-content>, flow cytometry and immunofluorescence experiments whereas activation of STAT3 was less strong in <jats:styled-content style=\"fixed-case\">EMSA<\/jats:styled-content>, but strong in flow cytometry and immunofluorescence. Human recombinant IL\u20106 activated STAT3 and human IL\u20104 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\u2010\u03b1 had an inhibitory effect on porcine ocular cells in proliferation assays.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our study demonstrated that some types of human cytokines and interferon activate intracellular JAK\u2010STAT signaling pathways in porcine ocular cells. We hypothesize that direct stimulation of the JAK\u2010STAT pathway in porcine cells in response to human cytokines will lead to complications or failure, if pig\u2010to\u2010human ocular tissue xenotransplantation were to be carried out. For successful xenotransplantation among other obstacles there must be new approaches developed to regulate signaling pathways.<\/jats:p><\/jats:sec>","DOI":"10.1111\/xen.12070","type":"journal-article","created":{"date-parts":[[2013,11,1]],"date-time":"2013-11-01T13:01:09Z","timestamp":1383310869000},"page":"469-480","source":"Crossref","is-referenced-by-count":12,"title":["Human cytokines activate JAK\u2013STAT signaling pathway in porcine ocular tissue"],"prefix":"10.1111","volume":"20","author":[{"given":"Elizaveta","family":"Fasler\u2010Kan","sequence":"first","affiliation":[{"name":"Department of Biomedicine University of Basel and University Hospital Basel Basel Switzerland"},{"name":"Institute of Chemistry and Bioanalytics University of Applied Sciences Northwestern Switzerland Muttenz Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natasha S.","family":"Barteneva","sequence":"additional","affiliation":[{"name":"Program in Cellular and Molecular 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