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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 histopathology of the spleen and joints of CIA mice. A photomicrograph of joint histopathology showing synoviocyte hyperplasia (arrow a), blood vessels (arrow b), articular cartilage destruction and pannus (arrow c). A photomicrograph of spleen histopathology showing red pulp congestion (arrow a), white pulp proliferation (arrow b) and germinal center formation (arrow c) (A). Effects of C-K on joint histopathology (B). Effects of C-K on spleen histopathology (C). Mean±SD. n=10. bP<0.05, cP<0.01 vs CIA mice.
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fig3: Effects of C-K on the histopathology of the spleen and joints of CIA mice. A photomicrograph of joint histopathology showing synoviocyte hyperplasia (arrow a), blood vessels (arrow b), articular cartilage destruction and pannus (arrow c). A photomicrograph of spleen histopathology showing red pulp congestion (arrow a), white pulp proliferation (arrow b) and germinal center formation (arrow c) (A). Effects of C-K on joint histopathology (B). Effects of C-K on spleen histopathology (C). Mean±SD. n=10. bP<0.05, cP<0.01 vs CIA mice.

Mentions: In CIA mice, synoviocytes proliferated to multiple layers, and the articular cartilage was destroyed and demonstrated inflammatory infiltration. The hyperplastic synovium in CIA mice included a large number of fibroblasts and new blood vessels. In mice treated with C-K (56 mg/kg), articular cartilage destruction and pannus formation were slightly inhibited. C-K (112 mg/kg) significantly reduced articular cartilage destruction, pannus formation, and synovial hyperplasia, although inflammatory cell infiltration was observed to a small extent (Figure 3A). The inflammatory scores of the joints in the model mice were increased in comparison with those of normal mice. C-K (56 and 112 mg/kg) and MTX (2 mg/kg) substantially rescued the increase in inflammatory scores observed in CIA mice (Figure 3B).


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 histopathology of the spleen and joints of CIA mice. A photomicrograph of joint histopathology showing synoviocyte hyperplasia (arrow a), blood vessels (arrow b), articular cartilage destruction and pannus (arrow c). A photomicrograph of spleen histopathology showing red pulp congestion (arrow a), white pulp proliferation (arrow b) and germinal center formation (arrow c) (A). Effects of C-K on joint histopathology (B). Effects of C-K on spleen histopathology (C). Mean±SD. n=10. bP<0.05, cP<0.01 vs CIA mice.
© Copyright Policy
Related In: Results  -  Collection

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

fig3: Effects of C-K on the histopathology of the spleen and joints of CIA mice. A photomicrograph of joint histopathology showing synoviocyte hyperplasia (arrow a), blood vessels (arrow b), articular cartilage destruction and pannus (arrow c). A photomicrograph of spleen histopathology showing red pulp congestion (arrow a), white pulp proliferation (arrow b) and germinal center formation (arrow c) (A). Effects of C-K on joint histopathology (B). Effects of C-K on spleen histopathology (C). Mean±SD. n=10. bP<0.05, cP<0.01 vs CIA mice.
Mentions: In CIA mice, synoviocytes proliferated to multiple layers, and the articular cartilage was destroyed and demonstrated inflammatory infiltration. The hyperplastic synovium in CIA mice included a large number of fibroblasts and new blood vessels. In mice treated with C-K (56 mg/kg), articular cartilage destruction and pannus formation were slightly inhibited. C-K (112 mg/kg) significantly reduced articular cartilage destruction, pannus formation, and synovial hyperplasia, although inflammatory cell infiltration was observed to a small extent (Figure 3A). The inflammatory scores of the joints in the model mice were increased in comparison with those of normal mice. C-K (56 and 112 mg/kg) and MTX (2 mg/kg) substantially rescued the increase in inflammatory scores observed in CIA mice (Figure 3B).

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