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Ginsenoside compound K suppresses the abnormal activation of T lymphocytes in mice with collagen-induced arthritis.

Liu KK, Wang QT, Yang SM, Chen JY, Wu HX, Wei W - Acta Pharmacol. Sin. (2014)

Bottom Line: 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.Methotrexate treatment exerted comparable effects in all these experiments.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.

View Article: PubMed Central - PubMed

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.

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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Related in: MedlinePlus

Effects of C-K on the expression of CD28, TCR, CTLA-4, and PD-1 on the T lymphocytes of CIA mice. T lymphocytes were isolated using magnetic beads. The result was representative of those from three experiments (A and B). Laser confocal microscopy demonstrated changes in CD28, TCR, CTLA-4, and PD-1 expression similar to Western blotting (C). Mean±SD. n=10. cP<0.01 vs normal mice. fP<0.01 vs CIA mice.
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fig7a: Effects of C-K on the expression of CD28, TCR, CTLA-4, and PD-1 on the T lymphocytes of CIA mice. T lymphocytes were isolated using magnetic beads. The result was representative of those from three experiments (A and B). Laser confocal microscopy demonstrated changes in CD28, TCR, CTLA-4, and PD-1 expression similar to Western blotting (C). Mean±SD. n=10. cP<0.01 vs normal mice. fP<0.01 vs CIA mice.

Mentions: The activation and differentiation of T lymphocytes are controlled by the expression of the TCR, CD28, CTLA-4, and PD-1. In this study, the expression of CD28 and the TCR in the T lymphocytes of CIA mice increased, whereas the levels of CTLA-4 and PD-1 in T lymphocytes was significantly decreased (Figure 7A). Compared with the CIA mice, C-K greatly decreased the expression of CD28 and the TCR, whereas it significantly increased the expression of CTLA-4 and PD-1 (Figure 7B). To verify this result, we used a laser confocal microscope to determine the expression of these important signaling molecules, which are involved in the activation of T lymphocytes. In accordance with the Western blot analysis, both the CD28 and TCR expression levels were increased on T cells isolated from CIA mice, whereas CTLA-4 and PD-1 expression decreased. Compared with T lymphocytes from CIA mice, those from C-K-treated mice (112 mg/kg) showed decreased expression of CD28 and the TCR, whereas CTLA-4 and PD-1 expression was significantly increased (Figure 7C).


Ginsenoside compound K suppresses the abnormal activation of T lymphocytes in mice with collagen-induced arthritis.

Liu KK, Wang QT, Yang SM, Chen JY, Wu HX, Wei W - Acta Pharmacol. Sin. (2014)

Effects of C-K on the expression of CD28, TCR, CTLA-4, and PD-1 on the T lymphocytes of CIA mice. T lymphocytes were isolated using magnetic beads. The result was representative of those from three experiments (A and B). Laser confocal microscopy demonstrated changes in CD28, TCR, CTLA-4, and PD-1 expression similar to Western blotting (C). Mean±SD. n=10. cP<0.01 vs normal mice. fP<0.01 vs CIA mice.
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Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4814039&req=5

fig7a: Effects of C-K on the expression of CD28, TCR, CTLA-4, and PD-1 on the T lymphocytes of CIA mice. T lymphocytes were isolated using magnetic beads. The result was representative of those from three experiments (A and B). Laser confocal microscopy demonstrated changes in CD28, TCR, CTLA-4, and PD-1 expression similar to Western blotting (C). Mean±SD. n=10. cP<0.01 vs normal mice. fP<0.01 vs CIA mice.
Mentions: The activation and differentiation of T lymphocytes are controlled by the expression of the TCR, CD28, CTLA-4, and PD-1. In this study, the expression of CD28 and the TCR in the T lymphocytes of CIA mice increased, whereas the levels of CTLA-4 and PD-1 in T lymphocytes was significantly decreased (Figure 7A). Compared with the CIA mice, C-K greatly decreased the expression of CD28 and the TCR, whereas it significantly increased the expression of CTLA-4 and PD-1 (Figure 7B). To verify this result, we used a laser confocal microscope to determine the expression of these important signaling molecules, which are involved in the activation of T lymphocytes. In accordance with the Western blot analysis, both the CD28 and TCR expression levels were increased on T cells isolated from CIA mice, whereas CTLA-4 and PD-1 expression decreased. Compared with T lymphocytes from CIA mice, those from C-K-treated mice (112 mg/kg) showed decreased expression of CD28 and the TCR, whereas CTLA-4 and PD-1 expression was significantly increased (Figure 7C).

Bottom Line: 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.Methotrexate treatment exerted comparable effects in all these experiments.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.

View Article: PubMed Central - PubMed

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.

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.

Show MeSH
Related in: MedlinePlus