Tetrandrine attenuates dendritic cell-mediated alloimmune responses and prolongs graft survival in mice.
Tetrandrine, a bisbenzylisoquinoline alkaloid, has significant immunosuppressive effects; however, the effects of tetrandrine on dendritic cells (DCs) and the associated immune reactions are unclear. In this study, we investigated the effects of tetrandrine on DCs and the effects of the tetrandrine-treated DCs on alloimmune reactions in vitro and graft survival in vivo. Tetrandrine significantly downregulated the expression of CD80 and CD86 of DCs and increased their secretion of IL-10 (p = 0.0001). Mixed leukocyte reaction showed that tetrandrine inhibited dendritic-cell allo-stimulatory activity, which was reversed by the anti-IL-10 treatment. An in vivo study demonstrated that tetrandrine-treated DCs prolonged the survival time of skin grafts in mice compared to control (p = 0.005) and decreased cellular infiltration of the graft in the histopathological study. The data suggest that tetrandrine-treated DCs cause immunosuppression and protect skin grafts from rejection. The tetrandrine-induced immunosuppression seems to be partially due to increased IL-10 secretion.
Chen
Yun
Y
Department of Surgery, Far Eastern Memorial Hospital, Taipei, Taiwan.
Lai
Hong-Shiee
HS
Chiang
Bor-Luen
BL
Tseng
Sheng-Hong
SH
Chen
Wei-Jao
WJ
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D044182:Benzylisoquinolines / Q000494:pharmacology*; D003713:Dendritic Cells / Q000378:metabolism*; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D006085:Graft Survival / Q000187:drug effects* / Q000276:immunology; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D016753:Interleukin-10 / Q000378:metabolism; D007962:Leukocytes / Q000187:drug effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018517:Plant Roots; D012867:Skin / Q000187:drug effects / Q000276:immunology; D016038:Skin Transplantation / Q000276:immunology / Q000379:methods*; D031607:Stephania / Q000737:chemistry*; D014181:Transplantation Immunology / Q000187:drug effects
D015703:Antigens, CD; D044182:Benzylisoquinolines; D004365:Drugs, Chinese Herbal; D007166:Immunosuppressive Agents; D016753:Interleukin-10; C009438:tetrandrine