(5R)-5-hydroxytriptolide (LLDT-8), a novel triptolide derivative, prevents experimental autoimmune encephalomyelitis via inhibiting T cell activation

被引:35
作者
Fu, Yun-Feng
Zhu, Yi-Na
Ni, Jia
Zhong, Xiang-Gen
Tang, Wei
Zhou, Ru
Zhou, Yu
Dong, Jia-Rong
He, Pei-Lan
Wan, Hua
Li, Yuan-Chao
Yang, Yi-Fu
Zuo, Jian-Ping
机构
[1] Chinese Acad Sci, Shanghai Inst Materia Med, Lab Immunopharmacol, Shanghai 201203, Peoples R China
[2] Chinese Acad Sci, Shanghai Inst Materia Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
[3] Shanghai Univ Tradit Chinese Med, Shu Guang Hosp, Shanghai, Peoples R China
关键词
(5R)-5-hydroxytriptolide; experimental autommume encephalomyelitis; T cell; cytokine;
D O I
10.1016/j.jneuroim.2006.03.011
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
A novel triptolide derivative (5R)-5-hydroxytriptolide (LLDT-8) has been shown to have potent inummosuppressive activities. Here LLDT-8 was evaluated in experimental autoimmune encephalomyelitis (EAE), the model of multiple sclerosis (MS). LLDT-8 reduced the incidence and severity of EAE, which was associated with the inhibition of the MOG 35-55 lymphocyte recall response, anti-MOG 35-55 T cell responses, interleukin (IL)-2 and interferon (IFN)-gamma production. In vitro, LLDT-8 inhibited primary T cells proliferation, division, IL-2 and IFN-gamma production stimulated with anti-CD3/28. These findings highlight the fact that LLDT-8 prevents EAE by suppressing T cell proliferation and activation, with a potential for treatment of MS. (c) 2006 Published by Elsevier B.V.
引用
收藏
页码:142 / 151
页数:10
相关论文
共 40 条
[1]   Treatment of relapsing paralysis in experimental encephalomyelitis by targeting Th1 cells through atorvastatin [J].
Aktas, O ;
Waiczies, S ;
Smorodchenko, A ;
Dörr, J ;
Seeger, B ;
Prozorovski, T ;
Sallach, S ;
Endres, M ;
Brocke, S ;
Nitsch, R ;
Zipp, F .
JOURNAL OF EXPERIMENTAL MEDICINE, 2003, 197 (06) :725-733
[2]   Differential signaling by lymphocyte antigen receptors [J].
AlberolaIla, J ;
Takaki, S ;
Kerner, JD ;
Perlmutter, RM .
ANNUAL REVIEW OF IMMUNOLOGY, 1997, 15 :125-154
[3]   CYTOKINES IN THE CENTRAL-NERVOUS-SYSTEM OF MICE DURING CHRONIC RELAPSING EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS [J].
BAKER, D ;
ONEILL, JK ;
TURK, JL .
CELLULAR IMMUNOLOGY, 1991, 134 (02) :505-510
[4]  
Boubenider S, 1997, J NEPHROL, V10, P136
[5]  
Bright JJ, 1999, J IMMUNOL, V162, P6255
[6]   CONTINGENT GENETIC REGULATORY EVENTS IN LYMPHOCYTE-T ACTIVATION [J].
CRABTREE, GR .
SCIENCE, 1989, 243 (4889) :355-361
[7]   Sodium channels contribute to microglia/macrophage activation and function in EAE and MS [J].
Craner, MJ ;
Damarjian, TG ;
Liu, SJ ;
Hains, BC ;
Lo, AC ;
Black, JA ;
Newcombe, J ;
Cuzner, ML ;
Waxman, SG .
GLIA, 2005, 49 (02) :220-229
[8]   HOW MANY PEOPLE IN THE WORLD HAVE MULTIPLE-SCLEROSIS [J].
DEAN, G .
NEUROEPIDEMIOLOGY, 1994, 13 (1-2) :1-7
[9]   S-adenosyl-L-homocysteine hydrolase inactivation curtails ovalbumin-induced immune responses [J].
Fu, YF ;
Wang, JX ;
Zhao, Y ;
Yang, Y ;
Tang, W ;
Ni, J ;
Zhu, YN ;
Zhou, R ;
He, PL ;
Li, C ;
Li, XY ;
Yang, YF ;
Lawson, BR ;
Zuo, JP .
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 2006, 316 (03) :1229-1237
[10]  
Hikim APS, 2000, J ANDROL, V21, P431