Takei Masao, Umeyama Akemi, Arihara Shigenobu, Matsumoto Hitoshi
Division of Cellular Allergology, Research Center Borstel, Parkallee 22, D-23845, Borstel, Germany.
J Pharm Sci. 2005 May;94(5):974-82. doi: 10.1002/jps.20279.
Piceatannol is an anti-inflammatory, immunomodulatory, and antiproliferative stilbene that has been shown to interfere with the cytokine signaling pathway. Dendritic cells (DCs) play a pivotal in the initiation of T-cell-mediated immune responses, making them an attractive cellular adjuvant for use in cancer vaccines. This study investigated the effect of piceatannol on the phenotypic and functional maturation of human monocyte-derived DCs in vitro. Human monocytes were cultured with GM-CSF and IL-4 for 6 days, followed by another 2 days in the presence of piceatannol or LPS. DCs harvested on day 8 were examined using functional assays. The expression levels of CD1a, CD80, CD83, and CD86 as expressed by mean fluorescence intensity (MFI) on DCs differentiated from immature DCs after culture with 1 muM of piceatannol for 2 days were enhanced and decreased endocytic activity. Piceatannol-treated DCs also displayed enhanced T-cell stimulatory capacity in a MLR, as measured by T-cell proliferation. Similar results were obtained with DCs differentiated with LPS from immature DCs. However, piceatannol did not inhibit phenotypic and functional maturation induced by LPS from immature DCs. Piceatannol-treated DCs induced the differentiation of naive T cells towards a helper T-cell type 1 (Th1) response at DCs/T (1:5) cells ratio depending on IL-12 secretion. These results demonstrate that piceatannol may be used on DC-based vaccine for cancer immunotherapy.
白皮杉醇是一种具有抗炎、免疫调节和抗增殖作用的芪类化合物,已被证明可干扰细胞因子信号通路。树突状细胞(DCs)在T细胞介导的免疫反应启动中起关键作用,使其成为癌症疫苗中一种有吸引力的细胞佐剂。本研究调查了白皮杉醇对人单核细胞衍生的DCs在体外的表型和功能成熟的影响。将人单核细胞与GM-CSF和IL-4培养6天,然后在存在白皮杉醇或LPS的情况下再培养2天。在第8天收获的DCs使用功能测定法进行检查。在用1μM白皮杉醇培养2天后,从不成熟DCs分化而来的DCs上,通过平均荧光强度(MFI)表达的CD1a、CD80、CD83和CD86的表达水平增强,内吞活性降低。用T细胞增殖测量,白皮杉醇处理的DCs在混合淋巴细胞反应(MLR)中也表现出增强的T细胞刺激能力。从不成熟DCs用LPS分化得到的DCs也得到了类似的结果。然而,白皮杉醇并不抑制从不成熟DCs用LPS诱导的表型和功能成熟。白皮杉醇处理的DCs在DCs/T(1:5)细胞比例下,根据IL-12的分泌,诱导初始T细胞向辅助性T细胞1型(Th1)反应分化。这些结果表明,白皮杉醇可用于基于DCs的癌症免疫治疗疫苗。