title: Ginsenoside compound K suppresses the abnormal activation of T lymphocytes in mice with collagen-induced arthritis.
abstract: OBJECTIVE
  To investigate the anti-arthritis and immunomodulatory activities of ginsenoside compound K (C-K) in mice with collagen-induced arthritis (CIA).
  
  
  METHODS
  DBA/1 mice with CIA were treated with C-K (28, 56 or 112 mg·kg(-1)·d(-1), ig) or the positive control methotrexate (2 mg/kg, ig, every 3 d) for 34 d. Splenic T and B lymphocytes were positively isolated using anti-CD3-coated magnetic beads or a pan B cell isolation kit. T lymphocyte subsets, and CD28, T cell receptor (TCR), cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) and programmed death-1 (PD-1) expression in purified splenic T lymphocytes were analyzed using flow cytometry, Western blotting and laser confocal microscopy.
  
  
  RESULTS
  C-K treatment significantly ameliorated the pathologic manifestations of CIA mice, remarkably inhibited T lymphocyte proliferation, and marginally inhibited the proliferation of B lymphocytes. C-K treatment significantly suppressed TNF-α and anti-CII antibody levels, and increased IFN-γ level in the joints of CIA mice, but did not alter IL-4 production. Treatment of CIA mice with C-K significantly decreased the percentages of activated T cells, co-stimulatory molecule-expressing T cells and effector memory T cells, and increased the frequencies of naive T cells and regulatory T cells. Furthermore, C-K treatment significantly decreased the expression of CD28 and TCR, whereas it increased the expression of CTLA-4 and PD-1 on T lymphocytes of CIA mice. Methotrexate treatment exerted comparable effects in all these experiments.
  
  
  CONCLUSIONS
  C-K suppresses the progression of CIA through regulating TCR, CD28, CTLA-4 and PD-1 expression, thus inhibiting the abnormal activation and differentiation of T lymphocytes.
authors.affiliation: Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Anti-inflammatory and Immune Medicine (Anhui Medical University), Ministry of Education, Hefei 230032, China.
authors.forename: Kang-kang
authors.initials: KK
authors.lastname: Liu
authors.affiliation: Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Anti-inflammatory and Immune Medicine (Anhui Medical University), Ministry of Education, Hefei 230032, China.
authors.forename: Qing-tong
authors.initials: QT
authors.lastname: Wang
authors.affiliation: Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Anti-inflammatory and Immune Medicine (Anhui Medical University), Ministry of Education, Hefei 230032, China.
authors.forename: Si-min
authors.initials: SM
authors.lastname: Yang
authors.affiliation: Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Anti-inflammatory and Immune Medicine (Anhui Medical University), Ministry of Education, Hefei 230032, China.
authors.forename: Jing-yu
authors.initials: JY
authors.lastname: Chen
authors.affiliation: Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Anti-inflammatory and Immune Medicine (Anhui Medical University), Ministry of Education, Hefei 230032, China.
authors.forename: Hua-xun
authors.initials: HX
authors.lastname: Wu
authors.affiliation: Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Anti-inflammatory and Immune Medicine (Anhui Medical University), Ministry of Education, Hefei 230032, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D018106:CD28 Antigens / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D060908:CTLA-4 Antigen / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D003094:Collagen / Q000276:immunology / Q000494:pharmacology*; D036145:Ginsenosides / Q000276:immunology / Q000494:pharmacology*; D007371:Interferon-gamma / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects* / Q000276:immunology; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D061026:Programmed Cell Death 1 Receptor / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013154:Spleen / Q000187:drug effects / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: D018106:CD28 Antigens; D017252:CD3 Complex; D060908:CTLA-4 Antigen; D036145:Ginsenosides; C491383:Pdcd1 protein, mouse; D061026:Programmed Cell Death 1 Receptor; D011948:Receptors, Antigen, T-Cell; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D007371:Interferon-gamma; D003094:Collagen
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