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- Title
The Synergistic Effect of Tautomycetin on Cyclosporine A-Mediated Immunosuppression in a Rodent Islet Allograft Model.
- Authors
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
- 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/CsAcotreated 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.
- Subjects
ANTIBIOTICS; CYCLOSPORINE; IMMUNOSUPPRESSION; IMMUNOSUPPRESSIVE agents; T cells; APOPTOSIS
- Publication
Molecular Medicine, 2010, Vol 16, Issue 7/8, p298
- ISSN
1076-1551
- Publication type
Article
- DOI
10.2119/molmed.2009.00099