Department of Clinical Laboratory, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Immunopharmacol Immunotoxicol. 2010 Dec;32(4):576-84. doi: 10.3109/08923971003586876. Epub 2010 Feb 4.
Polysaccharopeptide (PSP) was extracted from Coriolus versicolor, and has been proved to be a valuable adjuvant for the combination with chemotherapy or radiotherapy in the treatment of various cancers.
To understand the mechanism of PSP on immunomodulation, we examined gene expression and cytokine secretion associated with immunosignal-transduction signaling in human peripheral blood mononuclear cells (PBMCs).
cDNA microarray and cytokine antibody array were used to identify differential gene expression profiles and cytokines secretion of PBMCs in the presence or absence of PSP for 24 h. The expression of the key genes and proteins related to Toll-like receptor (TLR) signaling and its downstream pathway was determined by RT-PCR or Western blot.
Compared with the control group, PSP up-regulated 22 genes expression (such as IFN-γ, CXCL10, TLR4, TLR5) in 117 genes associated with TLR signaling. Twenty-three of genes (e.g., TLR9, TLR10, SARM1, TOLLIP) related with TLR signaling pathway were down-regulated in PBMCs under PSP treatments. Five of cytokines (GCSF, GM-CSF, IL-1α, IL-6, IFN-γ) were up-regulated more than 1.3 times by PSP. The mRNA levels of TRAM, TRIF, and TRAF6, which are the key molecules of TLR signaling pathway, were markedly increased (P < 0.05). Moreover, the protein level of TRAF6 was also markedly increased (P < 0.01).
PSP-regulated gene expression and cytokine secretion related to TLR signaling pathway in human PBMCs. Especially, TRAM-TRIF-TRAF6 subsignaling pathway of TLR may be one of the key associated signaling pathways in the immunomodulation of PSP.
云芝多糖（PSP）从云芝中提取，已被证明在各种癌症的化疗或放疗联合治疗中是一种有价值的佐剂。
为了了解 PSP 对免疫调节的作用机制，我们研究了 PSP 存在或不存在时人外周血单核细胞（PBMC）中与免疫信号转导信号相关的基因表达和细胞因子分泌。
使用 cDNA 微阵列和细胞因子抗体阵列来鉴定 PBMC 在存在或不存在 PSP 时的差异基因表达谱和细胞因子分泌情况，持续 24 小时。通过 RT-PCR 或 Western blot 测定与 Toll 样受体（TLR）信号及其下游途径相关的关键基因和蛋白质的表达。
与对照组相比，PSP 上调了 117 个与 TLR 信号相关的基因中 22 个基因的表达（如 IFN-γ、CXCL10、TLR4、TLR5）。在 PSP 处理下，PBMCs 中与 TLR 信号通路相关的 23 个基因（如 TLR9、TLR10、SARM1、TOLLIP）下调。五种细胞因子（GCSF、GM-CSF、IL-1α、IL-6、IFN-γ）的表达上调超过 1.3 倍。TLR 信号通路的关键分子 TRAM、TRIF 和 TRAF6 的 mRNA 水平显著增加（P<0.05）。此外，TRAF6 蛋白水平也显著增加（P<0.01）。
PSP 调节人 PBMC 中与 TLR 信号通路相关的基因表达和细胞因子分泌。特别是 TLR 信号的 TRAM-TRIF-TRAF6 亚信号通路可能是 PSP 免疫调节的关键相关信号通路之一。
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