Source:http://linkedlifedata.com/resource/pubmed/id/12817000
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
1
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| pubmed:dateCreated |
2003-6-20
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| pubmed:abstractText |
Immunostimulatory oligodeoxynucleotides (ODN) containing the CpG motif are being tested as immune adjuvants in many disease settings. Of the human PBMC examined, plasmacytoid dendritic cells (pDC) are a major source of type I IFN upon stimulation with CpG ODN. IFNs have numerous immunostimulatory effects, including the induction of TNF-related apoptosis-inducing ligand (TRAIL)/Apo-2L on monocytes, NK cells, and T cells. Importantly, IFN has also been linked to antitumor responses. Thus, we tested whether CpG ODN stimulation of PBMC led to TRAIL/Apo-2L-induced tumor cell death. When PBMC were stimulated with CpG ODN, TRAIL/Apo-2L-dependent tumor cell death was observed. Further examination of CpG ODN-stimulated PBMC revealed that TRAIL/Apo-2L expression was limited to CD14(+) cells, which, when depleted, led to a loss of the TRAIL/Apo-2L-mediated tumor cell killing. Moreover, pDC depletion also abolished the TRAIL/Apo-2L-mediated killing of tumor cell targets. Analysis of the pDC showed IFN-alpha production after CpG ODN stimulation. Finally, inclusion of neutralizing IFN-alpha antiserum with the PBMC during CpG ODN stimulation abrogated TRAIL/Apo-2L-mediated tumor cell killing. These results define a mechanism by which CpG ODN induces TRAIL/Apo-2L-dependent killing of tumor cells by CD14(+) PBMC, in which CpG ODN-activated pDC produce IFN-alpha that stimulates CD14(+) PBMC to express functional TRAIL/Apo-2L.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
AIM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD14,
http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Apoptosis Regulatory Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/CPG-oligonucleotide,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon-alpha,
http://linkedlifedata.com/resource/pubmed/chemical/Ligands,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Glycoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Oligodeoxyribonucleotides,
http://linkedlifedata.com/resource/pubmed/chemical/TNF-Related Apoptosis-Inducing...,
http://linkedlifedata.com/resource/pubmed/chemical/TNFSF10 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha
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| pubmed:status |
MEDLINE
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| pubmed:month |
Jul
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| pubmed:issn |
0022-1767
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:day |
1
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| pubmed:volume |
171
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
212-8
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| pubmed:dateRevised |
2006-11-15
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| pubmed:meshHeading |
pubmed-meshheading:12817000-Antigens, CD14,
pubmed-meshheading:12817000-Antineoplastic Agents,
pubmed-meshheading:12817000-Apoptosis,
pubmed-meshheading:12817000-Apoptosis Regulatory Proteins,
pubmed-meshheading:12817000-Cells, Cultured,
pubmed-meshheading:12817000-CpG Islands,
pubmed-meshheading:12817000-Cytotoxicity Tests, Immunologic,
pubmed-meshheading:12817000-Dendritic Cells,
pubmed-meshheading:12817000-Humans,
pubmed-meshheading:12817000-Interferon-alpha,
pubmed-meshheading:12817000-Leukocytes, Mononuclear,
pubmed-meshheading:12817000-Ligands,
pubmed-meshheading:12817000-Macrophages,
pubmed-meshheading:12817000-Melanoma,
pubmed-meshheading:12817000-Membrane Glycoproteins,
pubmed-meshheading:12817000-Monocytes,
pubmed-meshheading:12817000-Oligodeoxyribonucleotides,
pubmed-meshheading:12817000-Plasma Cells,
pubmed-meshheading:12817000-TNF-Related Apoptosis-Inducing Ligand,
pubmed-meshheading:12817000-Tumor Cells, Cultured,
pubmed-meshheading:12817000-Tumor Necrosis Factor-alpha
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| pubmed:year |
2003
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| pubmed:articleTitle |
Plasmacytoid dendritic cell-derived IFN-alpha induces TNF-related apoptosis-inducing ligand/Apo-2L-mediated antitumor activity by human monocytes following CpG oligodeoxynucleotide stimulation.
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| pubmed:affiliation |
Department of Urology, Interdisciplinary Graduate Program in Immunology, and Prostate Cancer Research Program of Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA 52242, USA.
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| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, Non-U.S. Gov't
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