The suppressive effect of triptolide on experimental autoimmune uveoretinitis by down-regulating Th1-type response.
We investigated the suppressive effect of triptolide (TRD), a purified component from a traditional Chinese herb, Tripterygium wilfordii Hook F. (TWHf), on uveitogenic peptide (K2)-induced experimental autoimmune uveoretinitis (EAU). K2-peptide immunized B10.A mice were divided into four groups. One group was EAU control which was treated with PBS. The other two groups were treated with TRD with different time courses (from day 0 to day 28 and from day 14 to day 28). The last group was treated with Cyclosporin A (CsA) as a positive control of the treatment. TRD was administered at dose of 0.1 mg/kg/day (i.p.). CsA was administered at dose of 20 mg/kg/day (i.p.) from day 0 to day 28 during whole period of EAU induction. The data showed that the EAU was suppressed in the whole period of TRD-treated mice, but was not in TRD-treated mice from day 14 to day 28 following immunization. The inhibition of EAU induced by TRD treatment was comparable to CsA-treated mice. The K2-specific lymphocyte proliferation and mRNA expressions of Th1-type cytokines (IL-12p40, IFN-gamma and TNF-alpha) in draining lymph node and inflamed eyes were reduced in TRD-treated mice. The K2-specific IFN-gamma production in the draining lymph node cells (LNC) of TRD-treated mice (whole period) was significantly inhibited. This effect was not related to an apoptotic effect of TRD on CD4+ T cells. Our results suggested that TRD suppressed the induction of EAU by down-regulating Th1-type response in B10.A mice. This preventive effect on EAU induction may be related to the inhibition of TRD on T cell priming and activation.
Wu
Yadi
Y
The Laboratory of Molecular Immunology, Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, PR China.
Wang
Yanping
Y
Zhong
Cuiping
C
Li
Yuanchao
Y
Li
Xiaoyu
X
Sun
Bing
B
D000818:Animals; D001327:Autoimmune Diseases / Q000188:drug therapy* / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D004195:Disease Models, Animal; D004224:Diterpenes / Q000008:administration & dosage / Q000627:therapeutic use*; D015536:Down-Regulation; D004852:Epoxy Compounds; D005260:Female; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D007274:Injections, Intraperitoneal; D051379:Mice; D008815:Mice, Inbred Strains; D010616:Phenanthrenes / Q000008:administration & dosage / Q000627:therapeutic use*; D012173:Retinitis / Q000188:drug therapy* / Q000276:immunology; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D014605:Uveitis / Q000188:drug therapy* / Q000276:immunology
D016207:Cytokines; D004224:Diterpenes; D004852:Epoxy Compounds; D007166:Immunosuppressive Agents; D010616:Phenanthrenes; C001899:triptolide