Poly-guanosine strings improve cellular uptake and stimulatory activity of phosphodiester CpG oligonucleotides in human leukocytes.
Vaccine
; 23(2): 148-55, 2004 Nov 25.
Article
em En
| MEDLINE
| ID: mdl-15531031
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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Base de dados:
MEDLINE
Assunto principal:
Oligodesoxirribonucleotídeos
/
Ativação Linfocitária
/
Guanosina
/
Leucócitos
Idioma:
En
Ano de publicação:
2004
Tipo de documento:
Article