rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
2003-10-24
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pubmed:abstractText |
Immunostimulatory activities of synthetic oligodeoxynucleotides containing CpG motifs (CpG-ODNs) have gained attention as potentially useful immunotherapeutics. However, CpG-ODNs induce harmful and lethal shock effects because they greatly enhance the sequence-dependent induction of tumor necrosis factor-alpha (TNF-alpha). We have shown that phosphorothioate-modified oligodeoxynucleotides (PS-ODNs) of the CpG-ODN 1826 stimulate TNF-alpha gene expression, TNF-alpha promoter activity, IkappaB degradation, and NF-kappaB activation at higher levels compared with its phosphodiester ODN (PO-ODN). In contrast to the effects of CpG-ODN 1826, PS-ODN of the CpG-ODN 2006 showed lower stimulatory activities than its PO-ODN. Using transient transfection, it was found that myeloid differentiation protein (MyD88) and tumor necrosis factor receptor-associated factor 6 are commonly required for activation of the TNF-alpha promoter by various CpG-ODNs with different potencies. These results strongly suggest a possibility to optimally activate the innate immune responses by modulating the potency of CpG-ODNs via sequence rearrangement and phosphorothioate backbone modification.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adaptor Proteins, Signal Transducing,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, Differentiation,
http://linkedlifedata.com/resource/pubmed/chemical/Myd88 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Myeloid Differentiation Factor 88,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/Oligodeoxyribonucleotides,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Immunologic,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
0006-291X
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
7
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pubmed:volume |
311
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
129-38
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:14575704-Adaptor Proteins, Signal Transducing,
pubmed-meshheading:14575704-Animals,
pubmed-meshheading:14575704-Antigens, Differentiation,
pubmed-meshheading:14575704-Cells, Cultured,
pubmed-meshheading:14575704-CpG Islands,
pubmed-meshheading:14575704-Gene Expression Regulation,
pubmed-meshheading:14575704-Macrophages,
pubmed-meshheading:14575704-Mice,
pubmed-meshheading:14575704-Myeloid Differentiation Factor 88,
pubmed-meshheading:14575704-NF-kappa B,
pubmed-meshheading:14575704-Oligodeoxyribonucleotides,
pubmed-meshheading:14575704-Receptors, Immunologic,
pubmed-meshheading:14575704-Tissue Distribution,
pubmed-meshheading:14575704-Tumor Necrosis Factor-alpha
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pubmed:year |
2003
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pubmed:articleTitle |
NF-kappaB-dependent regulation of tumor necrosis factor-alpha gene expression by CpG-oligodeoxynucleotides.
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pubmed:affiliation |
Institute of Life Science and Biotechnology, Yonsei University, Seoul, Republic of Korea.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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