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Human cytokines activate JAK‐STAT signaling pathways in porcine ocular tissue (LB214)
Author(s) -
FaslerKan Elizaveta,
Barteneva Natasha,
Nurzhanova Asil,
Wunderlich Kerstin,
Meyer Peter
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.lb214
Subject(s) - stat , flow cytometry , stat1 , cytokine , signal transduction , stat4 , stat protein , microbiology and biotechnology , jak stat signaling pathway , stat3 , biology , socs3 , immunofluorescence , stat6 , immunology , interleukin 4 , antibody , tyrosine kinase
The pig has been used extensively in experimental studies of human eye diseases. Pig retina shares many morphological features with the human eye. The use of porcine ocular cells (POC) as putative xenotransplants appears theoretically possible. We investigated cytokine‐induced changes of the JAK/STAT signaling pathways in POC in response to human cytokines. Methods POC were used to study the nuclear translocation of STAT proteins by gel‐shift assay, immunohistochemistry, confocal laser microscopy, flow and imaging cytometry. Results JAK/STAT signaling pathways could be activated in porcine pigmented epithelial ciliary body cells, pigmented iris epithelial cells and in lens epithelial cells in response to porcine and human cytokines. All POC showed very strong STAT1 activation upon stimulation with porcine interferon‐gamma. POC also respond to human cytokines; IFN‐alpha caused strong activation of STAT1 in all assays 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 POC with cytokines and interferons. Human IFN‐α had an inhibitory effect on POC in proliferation assays. Conclusion Our data demonstrate the upregulation of the members of the JAK‐STAT signaling pathway in POC . H uman cytokines and interferon activate JAK‐STAT signalling pathway in POC . We hypothesize that direct stimulation of the JAK‐STAT pathway in POC 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 signalling pathways.Grant Funding Source : University of Basel