Immunosuppressive effect of compound K on islet transplantation in a STZ-induced diabetic mouse model

  1. Zhong-Quan Qi1,*
  1. 1Organ Transplantation Institute, Medical College, Xiamen University, Xiamen City, Fujian Province, PR China
  2. 2Department of Thoracic Surgery, The First Affiliated Hospital of Xiamen University, Xiamen City, Fujian Province, PR China
  3. 3State Key Laboratory of Stress Cell Biology, School of Life Sciences, Xiamen University, Xiamen City, Fujian Province, PR China
  4. 4Department of Pathology, The Affiliated Chenggong Hospital of Xiamen University, Xiamen City, Fujian Province, PR China
  5. 5Department of Hepatobiliary Internal Medicine Clinic, The Affiliated Second Hospital of Fuzhou City of Xiamen University, Fuzhou City, Fujian Province, PR China
  6. 6School of Pharmaceutical Sciences, Guangxi Medical University, Nanning City, Guangxi Province, PR China
  1. *Corresponding Author: Jun-Jie Xia, E-mail: xia{at}xmu.edu.cn, or Zhong-Quan Qi, E-mail: oti{at}xmu.edu.cn.

Abstract

Islet transplantation is a therapeutic option for type 1 diabetes but its long-term success is limited by islet allograft survival. Many factors imperil islet survival, especially the adverse effects and toxicity due to clinical immunosuppressants. Compound K (Cpd K) is a synthesized analog of highly unsaturated fatty acids from Isatis tinctoria L. (Cruciferae). Here we investigated the therapeutic effect of Cpd K in diabetic mice and found that it significantly prolonged islet allograft survival with minimal adverse effects after 10 days. Furthermore, it reduced the proportion of CD4+ and CD8+ T cells in spleen and lymph nodes, inhibited lymphocyte infiltration in allografts, suppressed serum IL-2 and IFN-γ secretion, and increased TGF-β and Foxp3 mRNA expression. Surprisingly, Cpd K and rapamycin (Rapa) had a synergistic effect. Cpd K suppressed proliferation of naive T cells by inducing T cell anergy and promoting the generation of regulatory T cells (Tregs). In addition, NF-κB signaling was also blocked. Taken together, these findings indicate that Cpd K may have a potential immunosuppressant effective on islet transplantation.

Footnotes

  • # P-F M and J J contributed equally to this work.

  • Received January 3, 2014.
  • Accepted May 13, 2014.

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  1. Diabetes
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