Effects and mechanism of Glycyrrhiza inflata polysaccharides on the maturation and anti-tumor effect of dendritic cell
OBJECTIVE To investigate the effects and mechanism of Glycyrrhiza inflata polysaccharides(GiP)and GiP-B1 on the maturation and anti-tumor effect of dendritic cell(DC).METHODS The immature DC(imDC)of hepatocellular carcinoma cell H22 tumor-bearing mice cultured in vitro were divided into control group,tumor necrosis factor-α(TNF-α)group,GiP group,and GiP-B1 group.The viability,positive expressions of surface markers(CD11c,CD80,CD86,MHC-Ⅱ),the levels of interleukin-12p70(IL-12p70)and IL-4 in mature DC(mDC)of tumor-bearing mice were detected.mDC and CD4+T lymphocytes were co-cultured to generate CD4-cytotoxic T cell(CD4-CTL);stimulation index,the levels of IL-12p70,interferon-γ(IFN-γ),IL-4 and IL-10,the killing activity of CD4-CTL to H22 cell were detected.mRNA expressions of IL-12,IL-12 receptor(IL-12R),signal transducer and activator of transcription-4(STAT-4),as well as the protein expression of IL-12 receptor β2(IL-12Rβ2),phosphorylation levels of nuclear factor-kappa B(NF-κB)p65 and STAT-4 proteins in mDC were detected after co-culture.RESULTS Compared with the control group,the viability of mDC,the positive expressions of MHC-Ⅱ,and the levels of IL-12p70 and IL-4 were increased significantly in GiP group and GiP-B1 group(P＜0.05).The positive expressions of CD11c,CD80 and CD86 showed an increasing trend,but the differences were not statistically significant(P＞0.05).After co-culturing,the stimulation index,the levels of IL-12p70 and IFN-γ were significantly increased(P＜0.05),while the levels of IL-4 and IL-10(except for the GiP group)were significantly decreased(P＜0.05);the cytotoxicity against H22 cells was significantly enhanced(P＜0.05).mRNA expressions of IL-12 and IL-12R(except for GiP group)and STAT-4,protein expression of IL-12Rβ2 as well as phosphorylation levels of NF-κB p65 and STAT-4 protein were increased significantly in mDC(P＜0.05).CONCLUSIONS GiP and GiP-B1 have a good promoting effect on the maturation of DC in tumor-bearing mice,effectively stimulate CD4+T cell proliferation,enhance the anti-tumor activity of CD4-CTL,and its mechanism may be related to activating IL-12/NF-κB/STAT-4 signaling pathway.
Glycyrrhiza inflata polysaccharidesdendritic cellIL-12/NF-κB/STAT-4 signaling pathwaycytotoxic T lymphocytesanti-tumor
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