The synergistic effect of tautomycetin on cyclosporine a-mediated immunosuppression in a rodent islet allograft model

Yu Mee Wee, Monica Young Choi, Choong Hoon Kang, Yang Hee Kim, Jin Hee Kim, Sang Kyou Lee, Seung Young Yu, Song Cheol Kim, Duck Jong Han

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11 Citations (Scopus)

Abstract

Most immunosuppressive drugs that support successful allograft survival act by inhibiting or depleting T lymphocytes. Tautomycetin (TMC) is a specific inhibitor of protein phosphatase 1, which has a role in cell-cycle control and T-cell activation and promotes T-cell-specific apoptosis. In this study, we investigated the effect on rat islet transplantation of TMC alone and in combination with cyclosporine A (CsA). TMC treatment inhibited splenocyte proliferation in mixed lymphocyte reactions (MLR) without affecting cell viability. When used alone in islet allograft recipients, TMC did not significantly increase the survival of grafted islets. However, cotreatment of TMC and subtherapeutic doses of CsA significantly prolonged islet graft survival from 5.1 d to more than 100 d (P < 0.05). At 100 d, there was no evidence of specific organ toxicity, and histological analyses of grafted liver tissue revealed the presence of viable islets. CD4+ and CD8+ T-cell infiltration and interleukin (IL)-2 mRNA levels were decreased in TMC/CsA-cotreated rats, whereas IL-10 levels were increased. In addition, the number of FoxP3-expressing cells and FoxP3 mRNA levels were also increased. We suggest that CsA and TMC act synergistically to reduce the function of T-effector cells and enhance regulatory cell function in this islet allotransplantation model.

Original languageEnglish
Pages (from-to)298-306
Number of pages9
JournalMolecular Medicine
Volume16
Issue number7-8
DOIs
Publication statusPublished - 2010 Jul

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Genetics(clinical)

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    Wee, Y. M., Choi, M. Y., Kang, C. H., Kim, Y. H., Kim, J. H., Lee, S. K., Yu, S. Y., Kim, S. C., & Han, D. J. (2010). The synergistic effect of tautomycetin on cyclosporine a-mediated immunosuppression in a rodent islet allograft model. Molecular Medicine, 16(7-8), 298-306. https://doi.org/10.2119/molmed.2009.00099