title: Triptolide ameliorates autoimmune diabetes and prolongs islet graft survival in nonobese diabetic mice.
abstract: OBJECTIVE
  Triptolide (TPL) possesses profound immunosuppressive effects and has potential in allograft transplantation. We investigated whether TPL treatment prevents autoimmune diabetes in nonobese diabetic (NOD) mice and prolongs the survival of islet grafts against autoimmune attack or allograft rejection.
  
  
  METHODS
  Diabetic incidence was monitored in TPL-treated NOD mice. Nonobese diabetic or BALB/c islets were transplanted into diabetic recipients treated with TPL. Different T-cell subsets in grafts or spleen were analyzed. The proliferation, apoptosis, cytokines, and activities of AKT, NFκB, and caspases 3, 8, and 9 of T cells were determined.
  
  
  RESULTS
  Diabetic incidence was reduced and inflammatory cytokines were decreased in islets and spleen under TPL treatment. T-cell proliferation was reduced and the survival of syngeneic or allogeneic grafts was significantly increased in TPL-treated mice. The populations of CD4, CD8, CD4CD69, CD8CD69, and interferon-γ-producing T cells in islet grafts and spleen were reduced. Triptolide treatment increased the apoptosis of T cells in the spleen of recipients. Levels of phosphorylated protein kinase B and phosphorylated inhibitor of kappa B in splenocytes were reduced and caspases 3, 8, and 9 were increased in TPL-treated mice.
  
  
  CONCLUSIONS
  Triptolide treatment not only reduced the diabetic incidence in NOD mice but also prolonged the survival of syngeneic or allogeneic grafts.
authors.affiliation: Department of General Surgery, Tri-Service General Hospital, Taipei, Taiwan, Republic of China.
authors.forename: Shing-Hwa
authors.initials: SH
authors.lastname: Huang
authors.forename: Gu-Jiun
authors.initials: GJ
authors.lastname: Lin
authors.forename: Chi-Hong
authors.initials: CH
authors.lastname: Chu
authors.forename: Jyh-Cherng
authors.initials: JC
authors.lastname: Yu
authors.forename: Teng-Wei
authors.initials: TW
authors.lastname: Chen
authors.forename: Yuan-Wu
authors.initials: YW
authors.lastname: Chen
authors.forename: Ming-Wei
authors.initials: MW
authors.lastname: Chien
authors.forename: Chin-Chen
authors.initials: CC
authors.lastname: Chu
authors.forename: Huey-Kang
authors.initials: HK
authors.lastname: Sytwu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D015153:Blotting, Western; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D020169:Caspases / Q000276:immunology / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000517:prevention & control* / Q000601:surgery; D004224:Diterpenes / Q000494:pharmacology*; D004852:Epoxy Compounds / Q000494:pharmacology; D005260:Female; D005434:Flow Cytometry / Q000592:standards*; D006085:Graft Survival / Q000187:drug effects* / Q000276:immunology; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D007515:Islets of Langerhans / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D016381:Islets of Langerhans Transplantation / Q000276:immunology / Q000379:methods*; D051379:Mice; D008807:Mice, Inbred BALB C; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D016328:NF-kappa B / Q000276:immunology / Q000378:metabolism; D010616:Phenanthrenes / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000276:immunology / Q000378:metabolism; D013154:Spleen / Q000187:drug effects / Q000276:immunology / Q000378:metabolism
chemical_list: D016207:Cytokines; D004224:Diterpenes; D004852:Epoxy Compounds; D007166:Immunosuppressive Agents; D016328:NF-kappa B; D010616:Phenanthrenes; C001899:triptolide; D007371:Interferon-gamma; D051057:Proto-Oncogene Proteins c-akt; D020169:Caspases