Limits...
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.

Show MeSH

Related in: MedlinePlus

Effects of C-K on T and B lymphocyte proliferations in CIA mice. The data were described as the average of triplicate counts per minute (cpm) or quadruplicate optical densities. ConA induced T lymphocyte proliferation (A). LPS induced B lymphocyte proliferation (B). CII induced T lymphocyte proliferation in vitro (C). Mean±SD. n=10. bP<0.05 vs normal mice. eP<0.05, fP<0.01 vs CIA mice.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC4814039&req=5

fig4: Effects of C-K on T and B lymphocyte proliferations in CIA mice. The data were described as the average of triplicate counts per minute (cpm) or quadruplicate optical densities. ConA induced T lymphocyte proliferation (A). LPS induced B lymphocyte proliferation (B). CII induced T lymphocyte proliferation in vitro (C). Mean±SD. n=10. bP<0.05 vs normal mice. eP<0.05, fP<0.01 vs CIA mice.

Mentions: The results showed that the T and B lymphocyte proliferation induced by the different stimulators in CIA mice was increased compared with that in normal mice. C-K (28, 56, and 112 mg/kg) and MTX (2 mg/kg) clearly reduced ConA-induced T lymphocyte proliferation (Figure 4A). C-K (112 mg/kg) and MTX (2 mg/kg) mildly reduced LPS-induced B lymphocyte proliferation in CIA mice (Figure 4B). T lymphocyte proliferation induced by CII in CIA mice was increased compared with that in normal mice. Treatment with C-K (112 mg/kg) or MTX (2 mg/kg) reduced CII-induced T lymphocyte proliferation (Figure 4C). These data suggested that C-K primarily affects the function of T cells, but the characteristics and mechanism of C-K's effect need to be elucidated.


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 T and B lymphocyte proliferations in CIA mice. The data were described as the average of triplicate counts per minute (cpm) or quadruplicate optical densities. ConA induced T lymphocyte proliferation (A). LPS induced B lymphocyte proliferation (B). CII induced T lymphocyte proliferation in vitro (C). Mean±SD. n=10. bP<0.05 vs normal mice. eP<0.05, fP<0.01 vs CIA mice.
© Copyright Policy
Related In: Results  -  Collection

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

fig4: Effects of C-K on T and B lymphocyte proliferations in CIA mice. The data were described as the average of triplicate counts per minute (cpm) or quadruplicate optical densities. ConA induced T lymphocyte proliferation (A). LPS induced B lymphocyte proliferation (B). CII induced T lymphocyte proliferation in vitro (C). Mean±SD. n=10. bP<0.05 vs normal mice. eP<0.05, fP<0.01 vs CIA mice.
Mentions: The results showed that the T and B lymphocyte proliferation induced by the different stimulators in CIA mice was increased compared with that in normal mice. C-K (28, 56, and 112 mg/kg) and MTX (2 mg/kg) clearly reduced ConA-induced T lymphocyte proliferation (Figure 4A). C-K (112 mg/kg) and MTX (2 mg/kg) mildly reduced LPS-induced B lymphocyte proliferation in CIA mice (Figure 4B). T lymphocyte proliferation induced by CII in CIA mice was increased compared with that in normal mice. Treatment with C-K (112 mg/kg) or MTX (2 mg/kg) reduced CII-induced T lymphocyte proliferation (Figure 4C). These data suggested that C-K primarily affects the function of T cells, but the characteristics and mechanism of C-K's effect need to be elucidated.

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