AI Article Synopsis
- CpG-oligonucleotides activate the immune system by targeting Toll-like receptor 9 (TLR-9), but need to be taken up by cells first.
- 3'-poly-guanosine strings enhance the cellular uptake of phosphodiester CpG-ODN, leading to increased IL-6 secretion and better activation of immune cells.
- Phosphorothioate ODNs can still stimulate the immune response even without CpG motifs, demonstrating different mechanisms of action in immunology.
Article Abstract
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.
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| http://dx.doi.org/10.1016/j.vaccine.2004.05.020 | DOI Listing |
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