Mechanistic study of saikosaponin-d (Ssd) on suppression of murine T lymphocyte activation

Vincent Kam Wai Wong, Hua Zhou, Simon Shiu Fai Cheung, Ting Li, Liang LIU*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

62 Citations (Scopus)

Abstract

Saikosaponin-d (Ssd) is a triterpene saponin derived from the medicinal plant, Bupleurum falcatum L. (Umbelliferae). Previous findings showed that Ssd exhibits a variety of pharmacological and immunomodulatory activities including anti-inflammatory, anti-bacterial, antiviral and anti-cancer effects. In the current study we have investigated the effects of Ssd on activated mouse T lymphocytes through the NF-κB, NF-AT and AP-1 signaling pathways, cytokine secretion, and IL-2 receptor expression. The results demonstrated that Ssd not only suppressed OKT3/CD28-costimulated human T cell proliferation, it also inhibited PMA, PMA/Ionomycin and Con A-induced mouse T cell activation in vitro. The inhibitory effect of Ssd on PMA-induced T cell activation was associated with down-regulation of NF-κB signaling through suppression of IKK and Akt activities. In addition, Ssd suppressed both DNA binding activity and the nuclear translocation of NF-AT and activator protein 1 (AP-1) of the PMA/Ionomycin-stimulated T cells. The cell surface markers like IL-2 receptor (CD25) were also downregulated together with decreased production of pro-inflammatory cytokines of IL-6, TNF-α and IFN-γ. These results indicate that the NF-κB, NF-AT and AP-1 (c-Fos) signaling pathways are involved in the T cell inhibition evoked by Ssd, so it can be a potential candidate for further study in treating T cell-mediated autoimmune conditions.

Original languageEnglish
Pages (from-to)303-315
Number of pages13
JournalJournal of Cellular Biochemistry
Volume107
Issue number2
DOIs
Publication statusPublished - 15 May 2009

Scopus Subject Areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

User-Defined Keywords

  • AP-1
  • NF-κB
  • NF-AT
  • Saikosaponin-D
  • T lymphocyte activation

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