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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 differentiation of CD4+CD62L+CD44low and CD4+CD62L-CD44hi T lymphocytes in CIA mice. The population size of different T lymphocytes subsets was determined by flow cytometry. The percentages of the T lymphocyte subsets were analyzed by gating on lymphocytes. The number in each plots represents the expression of the subset of T cells among lymphocytes. Mean±SD. n=10. bP<0.05 vs normal mice. eP<0.05 vs CIA mice.
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fig6b: Effects of C-K on the differentiation of CD4+CD62L+CD44low and CD4+CD62L-CD44hi T lymphocytes in CIA mice. The population size of different T lymphocytes subsets was determined by flow cytometry. The percentages of the T lymphocyte subsets were analyzed by gating on lymphocytes. The number in each plots represents the expression of the subset of T cells among lymphocytes. Mean±SD. n=10. bP<0.05 vs normal mice. eP<0.05 vs CIA mice.

Mentions: The subgroups of T lymphocytes were examined by flow cytometry. The results showed that the percentages of CD3+CD4+ cells (analogous to helper T cells, Th cells), CD4+CD154+ cells (Th cells expressing co-stimulatory molecules CD154), CD4+CD69+ cells (analogous to activated T cells) and CD4+CD62L−CD44hi cells (analogous to effector memory T cells, TEM) in the spleens of CIA mice were significantly higher compared with those in normal mice, whereas the percentages of CD4+CD62L+CD44low cells (analogous to naive cells) and CD4+CD25+ Foxp3+ cells (analogous to regulatory T cells, Tregs) were significantly lower. C-K treatment decreased the proportions of CD4+CD154+, CD4+CD69+, and CD4+CD62L−CD44hi cells (Figures 6B, 6C, and 6D) and increased the percentages of CD4+CD62L+CD44low and CD4+CD25+ Foxp3+ cells (Figures 6B and 6F). The proportion of CD3+CD4+Th cells was not affected by C-K or MTX administration (Figure 6A). The data we obtained indicated that C-K substantially modulated the activation and differentiation of T lymphocytes in CIA mice, which might be a novel mechanism underlying the effects of C-K in the treatment of RA.


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 differentiation of CD4+CD62L+CD44low and CD4+CD62L-CD44hi T lymphocytes in CIA mice. The population size of different T lymphocytes subsets was determined by flow cytometry. The percentages of the T lymphocyte subsets were analyzed by gating on lymphocytes. The number in each plots represents the expression of the subset of T cells among lymphocytes. Mean±SD. n=10. bP<0.05 vs normal mice. eP<0.05 vs CIA mice.
© Copyright Policy
Related In: Results  -  Collection

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

fig6b: Effects of C-K on the differentiation of CD4+CD62L+CD44low and CD4+CD62L-CD44hi T lymphocytes in CIA mice. The population size of different T lymphocytes subsets was determined by flow cytometry. The percentages of the T lymphocyte subsets were analyzed by gating on lymphocytes. The number in each plots represents the expression of the subset of T cells among lymphocytes. Mean±SD. n=10. bP<0.05 vs normal mice. eP<0.05 vs CIA mice.
Mentions: The subgroups of T lymphocytes were examined by flow cytometry. The results showed that the percentages of CD3+CD4+ cells (analogous to helper T cells, Th cells), CD4+CD154+ cells (Th cells expressing co-stimulatory molecules CD154), CD4+CD69+ cells (analogous to activated T cells) and CD4+CD62L−CD44hi cells (analogous to effector memory T cells, TEM) in the spleens of CIA mice were significantly higher compared with those in normal mice, whereas the percentages of CD4+CD62L+CD44low cells (analogous to naive cells) and CD4+CD25+ Foxp3+ cells (analogous to regulatory T cells, Tregs) were significantly lower. C-K treatment decreased the proportions of CD4+CD154+, CD4+CD69+, and CD4+CD62L−CD44hi cells (Figures 6B, 6C, and 6D) and increased the percentages of CD4+CD62L+CD44low and CD4+CD25+ Foxp3+ cells (Figures 6B and 6F). The proportion of CD3+CD4+Th cells was not affected by C-K or MTX administration (Figure 6A). The data we obtained indicated that C-K substantially modulated the activation and differentiation of T lymphocytes in CIA mice, which might be a novel mechanism underlying the effects of C-K in the treatment of RA.

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