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Novel colchicine derivatives enhance graft survival after transplantation via suppression of T‐cell differentiation and activity
Author(s) -
Choi MonicaY,
Wee YuMee,
Kim YangHee,
Shin Sung,
Yoo SungEun,
Han DuckJong
Publication year - 2019
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.28510
Subject(s) - colchicine , cd8 , stat protein , activator (genetics) , transplantation , apoptosis , cancer research , pharmacology , chemistry , receptor , immunology , microbiology and biotechnology , biology , immune system , medicine , biochemistry , stat3
Immunosuppressants are crucial in organ transplantation but their side effects are a trade‐off for long‐term use. Colchicine has been shown to be effective in various diseases, albeit with many side effects. To enhance the immunosuppressive effects of colchicine, in addition to minimizing its side effects, we attempted to synthesize new colchicine derivatives (KR compounds). In rat cardiac and pancreatic islet allograft, long‐term graft survival was identified in KR compound‐treated groups. The use of cyclosporine A (CsA) or colchicine inhibited the CD3 + and CD4 + T‐cell proliferation, whereas KR compounds inhibited the CD8 + T cells as well as CD4 + T cells. KR compounds reduced the apoptosis, interleukin‐2 receptor expression, and signal transducer and activator of transcription 3 phosphorylation more than CsA. These results indicate that KR compounds have a potential therapeutic value as novel agents for prevention of graft deterioration by allograft of rejection.