Immunosuppressive effects of tautomycetin in vivo and in vitro via T cell-specific apoptosis induction

Jae Hyuck Shim, Heung Kyu Lee, Eun Ju Chang, Wook Jin Chae, Jin Hwan Han, Duck Jong Han, Tomohiro Morio, Jung Jin Yang, Alfred Bothwell, Sang Kyou Lee

Research output: Contribution to journalArticle

47 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)10617-10622
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume99
Issue number16
DOIs
Publication statusPublished - 2002 Aug 1

Fingerprint

Immunosuppressive Agents
Apoptosis
T-Lymphocytes
Cyclosporine
Caspase 1
Poly(ADP-ribose) Polymerases
src-Family Kinases
Caspase 9
Tacrolimus
Graft Survival
Caspase 3
Allografts
Tyrosine
Phosphorylation
Cell Proliferation
tautomycetin
In Vitro Techniques
Transplants

All Science Journal Classification (ASJC) codes

  • General

Cite this

Shim, Jae Hyuck ; Lee, Heung Kyu ; Chang, Eun Ju ; Chae, Wook Jin ; Han, Jin Hwan ; Han, Duck Jong ; Morio, Tomohiro ; Yang, Jung Jin ; Bothwell, Alfred ; Lee, Sang Kyou. / Immunosuppressive effects of tautomycetin in vivo and in vitro via T cell-specific apoptosis induction. In: Proceedings of the National Academy of Sciences of the United States of America. 2002 ; Vol. 99, No. 16. pp. 10617-10622.
@article{ff2ed6ec5ff0462eb09683b656b7dd2f,
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.",
author = "Shim, {Jae Hyuck} and Lee, {Heung Kyu} and Chang, {Eun Ju} and Chae, {Wook Jin} and Han, {Jin Hwan} and Han, {Duck Jong} and Tomohiro Morio and Yang, {Jung Jin} and Alfred Bothwell and Lee, {Sang Kyou}",
year = "2002",
month = "8",
day = "1",
doi = "10.1073/pnas.162522099",
language = "English",
volume = "99",
pages = "10617--10622",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "16",

}

Immunosuppressive effects of tautomycetin in vivo and in vitro via T cell-specific apoptosis induction. / Shim, Jae Hyuck; Lee, Heung Kyu; Chang, Eun Ju; Chae, Wook Jin; Han, Jin Hwan; Han, Duck Jong; Morio, Tomohiro; Yang, Jung Jin; Bothwell, Alfred; Lee, Sang Kyou.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 99, No. 16, 01.08.2002, p. 10617-10622.

Research output: Contribution to journalArticle

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 - 2002/8/1

Y1 - 2002/8/1

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.

UR - http://www.scopus.com/inward/record.url?scp=0036679005&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036679005&partnerID=8YFLogxK

U2 - 10.1073/pnas.162522099

DO - 10.1073/pnas.162522099

M3 - Article

C2 - 12149481

AN - SCOPUS:0036679005

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

SN - 0027-8424

IS - 16

ER -