Poly-guanosine strings improve cellular uptake and stimulatory activity of phosphodiester CpG oligonucleotides in human leukocytes

被引：34

作者：

Bartz, H ^{[1
]}

Mendoza, Y ^{[1
]}

Gebker, M ^{[1
]}

Fischborn, T ^{[1
]}

Heeg, K ^{[1
]}

Dalpke, A ^{[1
]}

机构：

[1] Univ Marburg, Inst Med Microbiol & Hyg, D-35037 Marburg, Germany

来源：

VACCINE | 2004年 / 23卷 / 02期

关键词：

CpG-oligonucleotides; immunostimulatory DNA; cellular uptake;

D O I：

10.1016/j.vaccine.2004.05.020

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

CpG-oligonucleotides (CpG-ODN) have been shown to exert strong immuno-stimulatory effects through activation of Toll-like receptor 9 (TLR-9). However, TLR-9 triggering takes place in endosomal compartments and thus CpG-ODN have to be taken up prior to signal transduction. We here report that 3'-poly-guanosine strings can improve cellular internalisation of phosphodiester but not of phosphorothioate CpG-ODN. Improved cellular uptake correlated with enhanced IL-6 secretion and proliferation of PBMC. Also, TLR-9 transfected HEK293 cells were activated more efficiently by poly-guanosine modified CpG-ODN. The results indicate that the synthesis of stimulatory CpG-ODN based on a phosphodiester backbone is feasible via such poly-guanosine substitutions. In addition we observed that phosphorothioate ODN were able to exert immunostimulatory effects independent of the presence of CpG motifs. (C) 2004 Elsevier Ltd. All rights reserved.

引用

页码：148 / 155

页数：8

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