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Triptolide inhibits the differentiation of Th17 cells and suppresses collagen-induced arthritis.

Authors
  • Wang, Y
  • Jia, L
  • Wu, C-Y
Type
Published Article
Journal
Scandinavian journal of immunology
Publication Date
Oct 01, 2008
Volume
68
Issue
4
Pages
383–390
Identifiers
DOI: 10.1111/j.1365-3083.2008.02147.x
PMID: 18782267
Source
Medline
License
Unknown

Abstract

Triptolide, a diterpenoid isolated from the Chinese herb Tripterygium wilfordii Hook F, has been demonstrated to be effective in the treatment of a variety of autoimmune diseases. T helper type 17 (Th17) cells represent a novel subset of CD4(+) T cells involved in the immunopathogenesis of autoimmune diseases. Currently, the effects of triptolide on the differentiation of Th17 cells remain unclear. Here, we found that triptolide significantly inhibited the generation of Th17 cells from murine splenocytes and purified CD4(+) T cells in a dose-dependent manner. The suppressive effects of triptolide were persistent even after it had been removed from cell cultures. Importantly, triptolide inhibited the transcription of interleukin-17 (IL-17) mRNA and IL-6-induced phosphorylation of STAT3, a key signalling molecule involved in the development of Th17 cells. Moreover, these suppressive effects of triptolide on Th17 differentiation were not due to cytotoxicity of triptolide because the numbers of viable cells had no significant difference between triptolide-treated and non-triptolide-treated cells. In vivo studies demonstrated that the treatment of collagen-induced arthritis (CIA) mice with triptolide reduced arthritis scores and swollen degree of joints. At the same time, the levels of collagen type II (CII)-specific IL-17 production and the percentages of CII-specific IL-17(+)CD4(+) T cells in the cells from draining lymph nodes and spleens were significantly reduced in CIA mice treated with triptolide. These results suggested that triptolide displayed an immunosuppressive effect on CIA by down-regulating CII-specific Th17 cells. Taken together, our results may provide a new light on the potential mechanism of the immunosuppressive and anti-inflammatory effects of triptolid.

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