Ginsenoside metabolite compound K suppresses T-cell priming via modulation of dendritic cell trafficking and costimulatory signals, resulting in alleviation of collagen-induced arthritis

Jingyu Chen, Huaxun Wu, Qingtong Wang, Yan Chang, Kangkang Liu, Wei Wei

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Ginsenosidemetabolite compound K (CK; 20-O-D-glucopyranosyl-20(S)-protopanaxadiol), a novel ginsenoside metabolite, belongs to the dammarane-type triterpene saponins, according to its structure. The anti-inflammatory activity of CK has been identified in several studies. Our study demonstrated that CK exerted an anti-inflammatory effect in collagen-induced arthritis (CIA) and adjuvant-induced arthritis animal models, and this effect was due to inhibition of the abnormal activation and differentiation of T cells. However, the mechanism of CK in suppressing T-cell activation remains unclear. In this study, CK had a therapeutic effect in mice with CIA, decreased the percentage of activated T cells and dendritic cells (DCs), and increased the percentage of naive T cells in lymph nodes. The inhibitory effect on T-cell activation of CK was related to suppression of accumulation of DCs in lymph nodes. CK decreased CCL21 levels in lymph nodes and CCR7 expression in DCs and suppressed CCL21/CCR7-mediated migration of DCs, thus reducing accumulation of DCs in lymph nodes. In addition, signals for T-cell activation including major histocompatibility complex class II and costimulatory molecules, such as CD80 and CD86, were suppressed by CK, and the proliferation of T cells induced by DCs was inhibited by CK. In conclusion, this study demonstrated that CK downregulated DC priming of T-cell activation in CIA, and suppression of CCL21/CCR7-mediated DC migration and signaling between T cells and DCs might be the potential mechanism. These results provide an interesting, novel insight into the potential mechanism by which CK contributes to the anti-inflammatory effect in autoimmune conditions.

Original languageEnglish (US)
Pages (from-to)71-79
Number of pages9
JournalJournal of Pharmacology and Experimental Therapeutics
Volume353
Issue number1
DOIs
StatePublished - Apr 1 2015
Externally publishedYes

Fingerprint

Experimental Arthritis
Dendritic Cells
T-Lymphocytes
Lymph Nodes
Anti-Inflammatory Agents
Ginsenosides
ginsenoside M1
Triterpenes
Saponins
Therapeutic Uses
Major Histocompatibility Complex
Cell Movement
Down-Regulation
Animal Models

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

Cite this

Ginsenoside metabolite compound K suppresses T-cell priming via modulation of dendritic cell trafficking and costimulatory signals, resulting in alleviation of collagen-induced arthritis. / Chen, Jingyu; Wu, Huaxun; Wang, Qingtong; Chang, Yan; Liu, Kangkang; Wei, Wei.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 353, No. 1, 01.04.2015, p. 71-79.

Research output: Contribution to journalArticle

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