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| Effects of a hexameric deoxyriboguanosine run conjugation into CpG oligodeoxynucleotides on their immunostimulatory potentials |
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| Author(s): Lee SW, Song MK, Baek KH, Park YJ, Kim JK, Lee CH, Cheong HK, Cheong C, Sung YC |
| Source: JOURNAL OF IMMUNOLOGY Volume: 165 Issue: 7 Pages: 3631-3639 Published: OCT 1 2000 |
| Times Cited: 54 References: 45 |
| Abstract: CpG oligodeoxynucleotides (ODNs) are promising immunomodulatory agents for treating human diseases and vaccine development. Phosphodiester CpG ODNs were demonstrated to have poor immunostimulatory potentials for cytokine production. However, the conjugation of consecutive deoxyriboguanosine residues, called a dG run, at the 3' terminus of phosphodiester CpG ODNs significantly enhanced TNF-alpha and IL-12 production from mouse splenic dendritic cells (DCs), The optimal induction of cytokine production was achieved by the addition of a hexameric dG (dG(6)) run, In contrast, the existence of a dG(6) run either at the 5' terminus of phosphodiester CpG ODNs or at the 3' terminus of phosphorothioate CpG ODNs diminished CpG-mediated cytokine induction, suggesting that the effects of a dG run depend on its location and the chemical property of the ODN backbone, respectively. In addition, we provided the evidence that the conjugation of a dG(6) run caused the structural transformation of CpG ODNs, which facilitates their targeting into mouse APCs such as splenic DCs, B cells, and peritoneal macrophages with a scavenger receptor type A ligand specificity. Among primary APCs, DCs were the most potent for CpG ODN-mediated IL-12 production. Furthermore, we demonstrated that the conjugation of a dG(6) run into the 3' terminus of phosphodiester CpG ODNs was crucial for their ability to generate Th1 immunity in vivo. Thus, the conjugation of a dG(6) run into phosphodiester CpG ODNs would be an alternative way to optimize their immunostimulatory potentials in vitro and in vivo. |
| Document Type: Article |
| Language: English |
| Reprint Address: Sung, YC (reprint author), Pohang Univ Sci & Technol, Dept Life Sci, Ctr Biofunct Mol, Pohang 790784, South Korea |
Addresses:
1. Pohang Univ Sci & Technol, Dept Life Sci, Ctr Biofunct Mol, Pohang 790784, South Korea
2. Korea Basic Sci Inst, Magnet Resonance Team, Taejon, South Korea |
| Publisher: AMER ASSOC IMMUNOLOGISTS, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA |
| Subject Category: Immunology |
| IDS Number: 357AZ |
| ISSN: 0022-1767 |
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