Immunosuppressive effect of compound K on islet transplantation in a STZ-induced diabetic mouse model
- Peng-Fei Ma1,#,
- Jie Jiang2,#,
- Chang Gao1,
- Pan-Pan Cheng1,
- Jia-Li Li1,
- Xin Huang1,
- Ying-Ying Lin1,
- Qing Li1,
- Yuan-Zheng Peng1,
- Mei-Chun Cai3,
- Wei Shao4,
- Qi Zhu5,
- Sai Han1,
- Qing Qin6,
- Jun-Jie Xia1,* and
- Zhong-Quan Qi1,*
- 1Organ Transplantation Institute, Medical College, Xiamen University, Xiamen City, Fujian Province, PR China
- 2Department of Thoracic Surgery, The First Affiliated Hospital of Xiamen University, Xiamen City, Fujian Province, PR China
- 3State Key Laboratory of Stress Cell Biology, School of Life Sciences, Xiamen University, Xiamen City, Fujian Province, PR China
- 4Department of Pathology, The Affiliated Chenggong Hospital of Xiamen University, Xiamen City, Fujian Province, PR China
- 5Department of Hepatobiliary Internal Medicine Clinic, The Affiliated Second Hospital of Fuzhou City of Xiamen University, Fuzhou City, Fujian Province, PR China
- 6School of Pharmaceutical Sciences, Guangxi Medical University, Nanning City, Guangxi Province, PR China
- *Corresponding Author: Jun-Jie Xia, E-mail: , or Zhong-Quan Qi, E-mail: .
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.
# P-F M and J J contributed equally to this work.
- Received January 3, 2014.
- Accepted May 13, 2014.
- © 2014 by the American Diabetes Association.
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