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The newly identified CpG-N ODN208 protects mice from challenge with CpG-S ODN by decreasing TNF-α release
- Source :
-
International Immunopharmacology . May2007, Vol. 7 Issue 5, p646-655. 10p. - Publication Year :
- 2007
-
Abstract
- Abstract: Administration of an excess of oligodeoxynucleotides containing immunostimulatory CpG motifs (CpG-S ODNs) may induce systemic inflammatory response syndrome (SIRS) and sepsis. Therefore, it is important to develop neutralizing CpG ODNs (CpG-N ODNs), which can be used to reduce the release of cytokines induced by the presence of CpG-S ODNs. In the present study, CpG-N ODN208 (5′-TGCCGCGGCAGA-3′), a neutralizing twelve-oligodeoxynucleotide molecule recently identified in our laboratory, inhibited TNF-α release from human peripheral blood mononuclear cells (hPBMCs) and murine RAW264.7 cells induced by CpG-S ODN exposure in a dose- and time-dependent manner. Flow cytometry revealed that CpG-N ODN208 decreased cell-surface binding and internalization of 6-FAM-CpG-S ODN. However, the decreased cell-surface binding and internalization of CpG-S ODN could not completely account for the decreased TNF-α release. RT-PCR experiments revealed that CpG-N ODN treatment could down-regulate the CpG-S ODN-induced upregulation of Toll-like receptor 9 (TLR9) mRNA expression. This finding suggested that the decreased cytokine release following CpG-N ODN treatment might be related to decreased TLR9 mRNA expression. In in vivo experiments, no protection was found when the ratio of CpG-N ODN to CpG-S ODN delivered to mice was 3:1. However, at a 5:1 ratio, CpG-N ODN208 could protect mice from an ordinarily lethal dose of CpG-S ODN. Furthermore, we found that CpG-N ODN208 treatment decreased serum TNF-α levels in mice injected with sublethal doses of CpG-S ODN whether the CpG-N ODN208 was added prior to or concurrent with the CpG-S ODN. Our results demonstrated that CpG-N ODN-mediated protection against a lethal challenge by CpG-S ODN was associated with the reduction of TNF-α release. [Copyright &y& Elsevier]
- Subjects :
- *SEPSIS
*CYTOKINES
*MOLECULES
*BLOOD cells
*CELL membranes
*THERAPEUTICS
Subjects
Details
- Language :
- English
- ISSN :
- 15675769
- Volume :
- 7
- Issue :
- 5
- Database :
- Academic Search Index
- Journal :
- International Immunopharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 24461186
- Full Text :
- https://doi.org/10.1016/j.intimp.2007.01.005