Enhanced immunostimulatory activity of oligodeoxynucleotides by Y-shape formation
Enhanced immunostimulatory activity of oligodeoxynucleotides by Y-shape formation
复制标题
DOI：
10.1111/j.1365-2567.2007.02762.x
复制
发表时间：
2008-06-01
期刊：
影响因子：
6.4
通讯作者：
Takakura, Yoshinobu
中科院分区：
文献类型：
--
作者：
Nishikawa, Makiya;Matono, Mitsuhiro;Takakura, Yoshinobu
含有未甲基化CpG二核苷酸（CpG DNA）的DNA是先天性和获得性免疫应答的有效激活剂。尽管CpG DNA的序列特异性免疫刺激活性已被广泛研究，但关于CpG DNA的立体化学性质的重要性的信息很少。在这项研究中，Y形寡脱氧核苷酸（Y-ODNs）的制备使用三个ODNs的一半是部分互补的其他两个ODNs的一半。Y-ODN比常规的单链ODN（ssODN）或双链ODN（dsODN）从RAW264.7巨噬细胞样细胞诱导更大量的肿瘤坏死因子-α和白细胞介素-6。Y-ODN在血清中的稳定性低于dsODN，但与dsODN相比，Y-ODN被巨噬细胞样细胞摄取的量更大。与含有相同序列的dsODN相比，新设计的含有三个有效CpG基序的Y-ODN产生显著更高水平的细胞因子。这些结果表明，Y型ODN是一种新的，可重复的和可靠的方法来增强ODN的免疫刺激活性。
DNA containing unmethylated CpG dinucleotides (CpG DNA) is a potent activator of innate and acquired immune responses. Although the sequence-specific immunostimulatory activity of CpG DNA has been extensively explored, little information is available about the importance of the stereochemical properties of CpG DNA. In this study, Y-shaped oligodeoxynucleotides (Y-ODNs) were prepared using three ODNs with the halves of each ODN being partially complementary to a half of the other two ODNs. Y-ODN induced greater amounts of tumour necrosis factor-alpha and interleukin-6 from RAW264.7 macrophage-like cells than did conventional single-stranded ODN (ssODN) or double-stranded ODN (dsODN). The Y-ODN was less stable in serum than dsODN, but greater amounts of Y-ODN were taken up by macrophage-like cells compared with dsODN. A newly designed Y-ODN containing three potent CpG motifs generated significantly higher levels of cytokines compared with dsODN containing the identical sequences. These results indicate that the Y-shaped form of ODN is a novel, reproducible and reliable approach to enhancing the immunostimulatory activity of ODNs.