TY - JOUR
T1 - Ginsenoside metabolite compound K suppresses T-cell priming via modulation of dendritic cell trafficking and costimulatory signals, resulting in alleviation of collagen-induced arthritis
AU - Chen, Jingyu
AU - Wu, Huaxun
AU - Wang, Qingtong
AU - Chang, Yan
AU - Liu, Kangkang
AU - Wei, Wei
PY - 2015/4/1
Y1 - 2015/4/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84923354889&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84923354889&partnerID=8YFLogxK
U2 - 10.1124/jpet.114.220665
DO - 10.1124/jpet.114.220665
M3 - Article
C2 - 25630466
AN - SCOPUS:84923354889
VL - 353
SP - 71
EP - 79
JO - Journal of Pharmacology and Experimental Therapeutics
JF - Journal of Pharmacology and Experimental Therapeutics
SN - 0022-3565
IS - 1
ER -