Immunosuppressive effect of compound K on islet transplantation in an STZ-induced diabetic mouse model.
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 (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 inflammatory cell infiltration in allografts, suppressed serum interleukin-2 and interferon-γ secretion, and increased transforming growth factor-β and Foxp3 mRNA expression. Surprisingly, Cpd K and rapamycin had a synergistic effect. Cpd K suppressed proliferation of naïve T cells by inducing T-cell anergy and promoting the generation of regulatory T cells. In addition, nuclear factor-κB signaling was also blocked. Taken together, these findings indicate that Cpd K may have a potential immunosuppressant effect on islet transplantation.
Organ Transplantation Institute, Medical College, Xiamen University, Xiamen City, Fujian Province, PR China.
Peng-Fei
PF
Ma
Department of Thoracic Surgery, The First Affiliated Hospital of Xiamen University, Xiamen City, Fujian Province, PR China.
Jie
J
Jiang
Organ Transplantation Institute, Medical College, Xiamen University, Xiamen City, Fujian Province, PR China.
Chang
C
Gao
Organ Transplantation Institute, Medical College, Xiamen University, Xiamen City, Fujian Province, PR China.
Pan-Pan
PP
Cheng
Organ Transplantation Institute, Medical College, Xiamen University, Xiamen City, Fujian Province, PR China.
Jia-Li
JL
Li
Organ Transplantation Institute, Medical College, Xiamen University, Xiamen City, Fujian Province, PR China.
Xin
X
Huang
Organ Transplantation Institute, Medical College, Xiamen University, Xiamen City, Fujian Province, PR China.
Ying-Ying
YY
Lin
Organ Transplantation Institute, Medical College, Xiamen University, Xiamen City, Fujian Province, PR China.
Qing
Q
Li
Organ Transplantation Institute, Medical College, Xiamen University, Xiamen City, Fujian Province, PR China.
Yuan-Zheng
YZ
Peng
State Key Laboratory of Stress Cell Biology, School of Life Sciences, Xiamen University, Xiamen City, Fujian Province, PR China.
Mei-Chun
MC
Cai
Department of Pathology, The Affiliated Chenggong Hospital of Xiamen University, Xiamen City, Fujian Province, PR China.
Wei
W
Shao
Department of Hepatobiliary Internal Medicine Clinic, The Affiliated Fuzhou Second Hospital of Xiamen University, Fuzhou City, Fujian Province, PR China.
Qi
Q
Zhu
Organ Transplantation Institute, Medical College, Xiamen University, Xiamen City, Fujian Province, PR China.
Sai
S
Han
School of Pharmaceutical Sciences, Guangxi Medical University, Nanning City, Guangxi Province, PR China.
Qing
Q
Qin
Organ Transplantation Institute, Medical College, Xiamen University, Xiamen City, Fujian Province, PR China xia@xmu.edu.cn oti@xmu.edu.cn.
Jun-Jie
JJ
Xia
Organ Transplantation Institute, Medical College, Xiamen University, Xiamen City, Fujian Province, PR China xia@xmu.edu.cn oti@xmu.edu.cn.
Zhong-Quan
ZQ
Qi
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000473:pathology / Q000601:surgery*; D036145:Ginsenosides / Q000494:pharmacology / Q000627:therapeutic use*; D006085:Graft Survival / Q000187:drug effects*; D007108:Immune Tolerance / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D007371:Interferon-gamma / Q000097:blood; D007376:Interleukin-2 / Q000097:blood; D016381:Islets of Langerhans Transplantation; D051379:Mice; D013154:Spleen / Q000187:drug effects / Q000473:pathology
D036145:Ginsenosides; D007166:Immunosuppressive Agents; D007371:Interferon-gamma; D007376:Interleukin-2; C112772:ginsenoside compound K