Polysaccharide purified from Ganoderma lucidum induced activation and maturation of human monocyte-derived dendritic cells by the NF-κB and p38 mitogen-activated protein kinase pathways
Polysaccharide purified from Ganoderma lucidum induced activation and maturation of human monocyte-derived dendritic cells by the NF-κB and p38 mitogen-activated protein kinase pathways
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DOI：
10.1189/jlb.0804481
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发表时间：
2005-08-01
影响因子：
5.5
通讯作者：
Chiang, BL
中科院分区：
文献类型：
--
作者：
Lin, YL;Liang, YC;Chiang, BL
灵芝，一种原产于中国的真菌，已被广泛用于促进中国人的健康和长寿。具有G的支链（1->6）-β-D-葡聚糖部分的多糖组分。灵芝（PS-G）具有抗肿瘤活性和激活自然杀伤细胞的作用。在这项研究中，我们研究了PS-G对人单核细胞来源的树突状细胞（DC）的影响。用PS-G处理DC导致细胞表面CD 80、CD 86、CD 83、CD 40、CD 54和人类白细胞抗原（HLA）-DR的表达增强，以及白细胞介素（IL）-12 p70、p40和IL-10的产生增强，以及IL-12 p35、p40和IL-10 mRNA的表达增强，并且DC的内吞能力被抑制。此外，用PS-G处理DC导致增强的T细胞刺激能力和增加的T细胞分泌干扰素-γ和IL-10。用针对Toll样受体（TLR）-4的抗体中和抑制了PS-G诱导的IL-12 p40和IL-10的产生，表明TLR-4在与PS-G孵育后在信号传导DC中起重要作用。进一步研究表明，PS-G能增强I kappa B（I kappa B）激酶抑制剂和核因子（NF）-κ B活性，并能增强I kappa B α和p38丝裂原活化蛋白激酶（MAPK）磷酸化。此外，Helenalin抑制NF-κ B和SB 98059抑制p38 MAPK可不同程度地阻止PS-G对CD 80、CD 86、CD 83、CD 40、CD 54和HLA-DR表达以及IL-12 p70、p40和IL-10产生的影响。总之，我们的数据表明，PS-G可以有效地促进未成熟DC的活化和成熟，这表明PS-G可能具有调节免疫反应的潜力。
Ganoderma lucidum, a fungus native to China, has been widely used to promote health and longevity in the Chinese. The polysaccharide component with a branched (1-->6)-beta-D-glucan moiety of G. lucidum (PS-G) has been reported to exert anti-tumor activity and activation of natural killer cells. In this study, we investigated the effects of PS-G on human monocyte-derived dendritic cells (DC). Treatment of DC with PS-G resulted in the enhanced cell-surface expression of CD80, CD86, CD83, CD40, CD54, and human leukocyte antigen (HLA)-DR, as well as the enhanced production of interleukin (IL)-12p70, p40, and IL-10 and also IL-12p35, p40, and IL-10 mRNA expression, and the capacity for endocytosis was suppressed in DC. In addition, treatment of DC with PS-G resulted in enhanced T cell-stimulatory capacity and increased T cell secretion of interferon-gamma and IL-10. Neutralization with antibodies against Toll-like receptor (TLR)-4 inhibited the PS-G-induced production of IL-12 p40 and IL-10, suggesting a vital role for TLR-4 in signaling DC upon incubation with PS-G. Further study showed that PS-G was able to augment inhibitor of kappa B (I kappa B) kinase and nuclear factor (NF)-kappa B activity and also I kappa B alpha and p38 mitogen-activated protein kinase (MAPK) phosphorylation. Further, inhibition of NF-kappa B by helenalin and p38 MAPK by SB98059 prevented the effects of PS-G in the expression of CD80, CD86, CD83, CD40, CD54, and HLA-DR and production of IL-12p70, p40, and IL-10 in various degrees. Taken together, our data demonstrate that PS-G can effectively promote the activation and maturation of immature DC, suggesting that PS-G may possess a potential in regulating immune responses.