(5R)-5-hydroxytriptolide (LLDT-8), a novel triptolide derivative, prevents experimental autoimmune encephalomyelitis via inhibiting T cell activation.
A novel triptolide derivative (5R)-5-hydroxytriptolide (LLDT-8) has been shown to have potent immunosuppressive 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.
Fu
Yun-Feng
YF
Laboratories of Immunopharmacology and Medicinal Chemistry, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, People's Republic of China.
Zhu
Yi-Na
YN
Ni
Jia
J
Zhong
Xiang-Gen
XG
Tang
Wei
W
Zhou
Ru
R
Zhou
Yu
Y
Dong
Jia-Rong
JR
He
Pei-Lan
PL
Wan
Hua
H
Li
Yuan-Chao
YC
Yang
Yi-Fu
YF
Zuo
Jian-Ping
JP
D000595:Amino Acid Sequence; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D004224:Diterpenes / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000517:prevention & control*; D004852:Epoxy Compounds; D005260:Female; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D008213:Lymphocyte Activation / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D010616:Phenanthrenes / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology
C509074:5-hydroxytriptolide; D004224:Diterpenes; D004852:Epoxy Compounds; D007166:Immunosuppressive Agents; D010616:Phenanthrenes; C001899:triptolide