TY - JOUR
T1 - Immunosuppressive effects of tautomycetin in vivo and in vitro via T cell-specific apoptosis induction
AU - Shim, Jae Hyuck
AU - Lee, Heung Kyu
AU - Chang, Eun Ju
AU - Chae, Wook Jin
AU - Han, Jin Hwan
AU - Han, Duck Jong
AU - Morio, Tomohiro
AU - Yang, Jung Jin
AU - Bothwell, Alfred
AU - Lee, Sang Kyou
PY - 2002/8
Y1 - 2002/8
N2 - Tautomycetin (TMC) was identified as an immunosuppressor of activated T cells. Inhibition of T cell proliferation with TMC was observed at concentrations 100-fold lower than those needed to achieve maximal inhibition with cyclosporin A (CsA). TMC specifically blocked tyrosine phosphorylation of intracellular signal mediators downstream of Src tyrosine kinases in a T cell-specific manner, leading to apoptosis due to cleavage of Bcl-2, caspase-9, caspase-3, and poly(ADP-ribose) polymerase, but not caspase-1. In TMC-treated rats that received a heterotopic cardiac allograft, the graft survived more than 160 days, comparable to graft survival in allografted rats treated with CsA. Thus, TMC, whose mechanism of action is different from that of CsA or FK506, can be used as a potent T cell-specific immunosuppressor.
AB - Tautomycetin (TMC) was identified as an immunosuppressor of activated T cells. Inhibition of T cell proliferation with TMC was observed at concentrations 100-fold lower than those needed to achieve maximal inhibition with cyclosporin A (CsA). TMC specifically blocked tyrosine phosphorylation of intracellular signal mediators downstream of Src tyrosine kinases in a T cell-specific manner, leading to apoptosis due to cleavage of Bcl-2, caspase-9, caspase-3, and poly(ADP-ribose) polymerase, but not caspase-1. In TMC-treated rats that received a heterotopic cardiac allograft, the graft survived more than 160 days, comparable to graft survival in allografted rats treated with CsA. Thus, TMC, whose mechanism of action is different from that of CsA or FK506, can be used as a potent T cell-specific immunosuppressor.
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U2 - 10.1073/pnas.162522099
DO - 10.1073/pnas.162522099
M3 - Article
C2 - 12149481
AN - SCOPUS:0036679005
SN - 0027-8424
VL - 99
SP - 10617
EP - 10622
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 16
ER -