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茯苓多糖通过 TLR4/TRAF6/NF-κB 信号通路在体外和体内发挥免疫调节作用。

Immunomodulatory effects exerted by Poria Cocos polysaccharides via TLR4/TRAF6/NF-κB signaling in vitro and in vivo.

机构信息

Department of Clinical Laboratory, the Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China.

The Second Clinic College, Chongqing Medical University, Chongqing 400010, China.

出版信息

Biomed Pharmacother. 2019 Apr;112:108709. doi: 10.1016/j.biopha.2019.108709. Epub 2019 Mar 1.

DOI:10.1016/j.biopha.2019.108709
PMID:30970514
Abstract

OBJECTIVE

Poria cocos polysaccharide (PCP) is the major active ingredients of P. cocos and possesses various pharmacological effects, including anti-oxidative and anti-apoptosis effects and activity against cancer. This study investigated the immunomodulatory mechanism by which PCP acts on RAW 264.7 macrophages and LLC tumors in mice.

METHODS

The concentrations of nitric oxide, and Th1, Th2, and Th17 cytokines were examined by Griess reaction and using a bead-based cytokine assessment kit. qRT-PCR and western blotting were used to investigate relevant signaling molecule expression.

RESULTS

Levels of nitric oxide, IL-2, IL-6, IL-17 A, TNF, and IFN-γ were increased by PCP while levels of IL-4 and IL-10 were unaffected. The addition of TAK-242 (TLR4 inhibitor) or assessment in C57BL/10ScNJ (TLR4-deficient) mice markedly reduced this effect. In C57BL/10 J (TLR4wild-type) mice, the indices of organ immune activity were all elevated, and oral PCP delivery resulted in a significant reduction in tumor volume over a 25 day period. Relative to controls, TLR4, MyD88, TRAF-6, p-NF-κB and p-c-JUN expression significantly increased, while TRAM expression did not change. Nevertheless, there was no PCP-dependent activation of MyD88, TRAF-6, TRAM, p-NF-κB or p-c-JUN in TLR4-deficient mice.

CONCLUSION

These results support the concept that PCP may exhibit immunomodulatory activity through TLR4/TRAF6/NF-κB signaling both in vitro and in vivo.

摘要

目的

茯苓多糖(PCP)是茯苓的主要活性成分,具有多种药理作用,包括抗氧化和抗凋亡作用以及抗癌作用。本研究探讨了 PCP 对 RAW 264.7 巨噬细胞和小鼠 LLC 肿瘤的免疫调节机制。

方法

通过格里塞反应和基于珠的细胞因子评估试剂盒检测一氧化氮和 Th1、Th2 和 Th17 细胞因子的浓度。使用 qRT-PCR 和 Western blot 检测相关信号分子的表达。

结果

PCP 增加了一氧化氮、IL-2、IL-6、IL-17A、TNF 和 IFN-γ的水平,而 IL-4 和 IL-10 的水平不受影响。添加 TAK-242(TLR4 抑制剂)或在 C57BL/10ScNJ(TLR4 缺陷)小鼠中评估显著降低了这种作用。在 C57BL/10J(TLR4 野生型)小鼠中,所有器官免疫活性指标均升高,口服 PCP 给药在 25 天内显著减少肿瘤体积。与对照组相比,TLR4、MyD88、TRAF-6、p-NF-κB 和 p-c-JUN 的表达显著增加,而 TRAM 的表达没有变化。然而,在 TLR4 缺陷型小鼠中,PCP 依赖性的 MyD88、TRAF-6、TRAM、p-NF-κB 或 p-c-JUN 激活不存在。

结论

这些结果支持 PCP 可能通过 TLR4/TRAF6/NF-κB 信号通路在体外和体内均具有免疫调节活性的观点。

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