title: Immunosuppressive effects of tautomycetin in vivo and in vitro via T cell-specific apoptosis induction.
abstract: 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.
authors.affiliation: Department of Biotechnology, College of Engineering and Bioproducts Research Center, Yonsei University, Seoul, Korea.
authors.forename: Jae-Hyuck
authors.initials: JH
authors.lastname: Shim
authors.forename: Heung-Kyu
authors.initials: HK
authors.lastname: Lee
authors.forename: Eun-Ju
authors.initials: EJ
authors.lastname: Chang
authors.forename: Wook-Jin
authors.initials: WJ
authors.lastname: Chae
authors.forename: Jin-Hwan
authors.initials: JH
authors.lastname: Han
authors.forename: Duck-Jong
authors.initials: DJ
authors.lastname: Han
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Morio
authors.forename: Jung-Jin
authors.initials: JJ
authors.lastname: Yang
authors.forename: Alfred
authors.initials: A
authors.lastname: Bothwell
authors.forename: Sang-Kyou
authors.initials: SK
authors.lastname: Lee
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D017209:Apoptosis; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D016572:Cyclosporine / Q000494:pharmacology; D005663:Furans; D006367:HeLa Cells; D016027:Heart Transplantation / Q000276:immunology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D019169:Jurkat Cells; D008055:Lipids; D008213:Lymphocyte Activation / Q000187:drug effects; D015394:Molecular Structure; D010766:Phosphorylation; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D017208:Rats, Wistar; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D014443:Tyrosine / Q000378:metabolism
chemical_list: D000935:Antifungal Agents; D005663:Furans; D007166:Immunosuppressive Agents; D008055:Lipids; D019253:Proto-Oncogene Proteins c-bcl-2; D017260:Receptor-CD3 Complex, Antigen, T-Cell; C058744:tautomycetin; D014443:Tyrosine; D016572:Cyclosporine; D011065:Poly(ADP-ribose) Polymerases; C505407:CASP3 protein, human; C506433:CASP9 protein, human; C505410:Casp3 protein, rat; C506435:Casp9 protein, rat; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases