Abstract
Aim:
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.
Conclusion:
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.
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Acknowledgements
This work was financially supported by the National Natural Science Foundation of China (30973543, 81173075, 81202541, and 81330081), the Anhui Provincial Natural Science Foundation (1208085QH146), the Grants for Scientific Research of BSKY (XJ201213), the Foundation for Young Academic Backbone of Anhui Medical University, and the Grants for Young Talents of Anhui Medical University (2013).
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Liu, Kk., Wang, Qt., Yang, Sm. et al. Ginsenoside compound K suppresses the abnormal activation of T lymphocytes in mice with collagen-induced arthritis. Acta Pharmacol Sin 35, 599–612 (2014). https://doi.org/10.1038/aps.2014.7
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DOI: https://doi.org/10.1038/aps.2014.7
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