title: Ginsenoside metabolite compound K suppresses T-cell priming via modulation of dendritic cell trafficking and costimulatory signals, resulting in alleviation of collagen-induced arthritis.
abstract: Ginsenoside metabolite 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.
authors: Institute of Clinical Pharmacology of Anhui Medical University and Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Hefei, China.
authors: Jingyu
authors: J
authors: Chen
authors: Institute of Clinical Pharmacology of Anhui Medical University and Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Hefei, China.
authors: Huaxun
authors: H
authors: Wu
authors: Institute of Clinical Pharmacology of Anhui Medical University and Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Hefei, China.
authors: Qingtong
authors: Q
authors: Wang
authors: Institute of Clinical Pharmacology of Anhui Medical University and Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Hefei, China.
authors: Yan
authors: Y
authors: Chang
authors: Institute of Clinical Pharmacology of Anhui Medical University and Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Hefei, China.
authors: Kangkang
authors: K
authors: Liu
authors: Institute of Clinical Pharmacology of Anhui Medical University and Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Hefei, China wwei@ahmu.edu.cn.
authors: Wei
authors: W
authors: Wei
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D018122:B7-1 Antigen / Q000378:metabolism; D051940:B7-2 Antigen / Q000378:metabolism; D002465:Cell Movement; D049109:Cell Proliferation; D054421:Chemokine CCL21 / Q000378:metabolism; D003094:Collagen; D003713:Dendritic Cells / Q000187:drug effects* / Q000502:physiology; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D008198:Lymph Nodes / Q000187:drug effects / Q000473:pathology; D008297:Male; D008811:Mice, Inbred DBA; D054400:Receptors, CCR7 / Q000378:metabolism; D012502:Sapogenins / Q000494:pharmacology* / Q000627:therapeutic use; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000473:pathology
chemical_list: C482402:20-O-(beta-D-glucopyranosyl)-20(S)-protopanaxadiol; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C515371:Ccr7 protein, mouse; D054421:Chemokine CCL21; D000949:Histocompatibility Antigens Class II; D054400:Receptors, CCR7; D012502:Sapogenins; D003094:Collagen