Angelan isolated from Angelica gigas Nakai induces dendritic cell maturation through toll-like receptor 4
Angelan isolated from Angelica gigas Nakai induces dendritic cell maturation through toll-like receptor 4
复制标题
DOI：
10.1016/j.intimp.2006.08.017
复制
发表时间：
2007-01-01
影响因子：
5.6
通讯作者：
Han, Sang-Bae
中科院分区：
文献类型：
--
作者：
Kim, Jee Youn;Yoon, Yeo Dae;Han, Sang-Bae
在肿瘤性疾病的发展过程中，树突状细胞（DC）的功能通常会减弱，这给基于DC的抗癌免疫疗法带来了问题。在这里，我们研究了当归多糖，一种从当归中分离的酸性多糖，对DC成熟的影响。Angelan有效地促进C5713 L/6和C3 H/HeN小鼠的tlr 4（+/+）DC的成熟，但不能促进C3 H/ReJ小鼠的tlr 4（-/-）DC的成熟。通过CD 80、CD 86和MHC-II类分子的表达升高证实了表型成熟，通过IL-12产生增加、同种异体T细胞刺激增强和内吞作用减少证实了功能成熟。发现Angelan激活ERK和NF-κ B，它们是Toll样受体-4（TLR 4）受体下游的信号分子。在同系小鼠肿瘤模型中，Angelan处理的成熟DC比未成熟DC更有效地抑制B16 F10肿瘤生长。这些结果表明angelan通过TLR 4信号通路诱导DC成熟，并表明angelan在基于DC的免疫疗法中的可能用途。(c)2006 Elsevier B. V.保留所有权利。
During the evolution of neoplastic diseases, dendritic cell (DC) functions are usually attenuated, and this presents a problem to DC-based immunotherapies against cancer. Here, we investigated the effects of angelan, an acidic polysaccharide isolated from Angelica gigas Nakai, on DC maturation. Angelan efficiently increased the maturation of tlr4(+/+) DCs from C5713L/6 and C3H/HeN mice, but not tlr4(-/-) DCs from C3H/ReJ mice. Phenotypic maturation was confirmed by the elevated expressions of CD80, CD86, and MHC-class II molecules, and functional maturation by increased IL-12 production, enhanced allogenic T cell stimulation, and decreased endocytosis. Angelan was found to activate ERK and NF-kappa B, which are signaling molecules downstream of toll-like receptor-4 (TLR4) receptors. Angelan-treated mature DC more effectively inhibited B16F10 tumor growth than immature DCs in syngenic murine tumor model. These results indicate that angelan induces DC maturation via TLR4 signaling pathways and suggest the possible use of angelan in DC-based immunotherapies. (c) 2006 Elsevier B.V. All rights reserved.