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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1-2
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pubmed:dateCreated |
2008-5-16
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pubmed:abstractText |
Drugs that target tumor necrosis factor-alpha (TNF) are particularly important in the treatment of severe inflammatory progression in rheumatoid arthritis, Crohn's disease and psoriasis. Despite the central role of the TNF/TNF receptor (TNFR) in various disease states, there is a paucity of information concerning TNFR2 signaling. In this study, we have developed a simple and highly sensitive cell-death based assay system for analyzing TNFR2-mediated bioactivity that can be used to screen for TNFR2-selective drugs. Using a lentiviral vector, a chimeric receptor was engineered from the extracellular and transmembrane domain of human TNFR2 and the intracellular domain of mouse Fas and the recombinant protein was then expressed in TNFR1(-/-)R2(-/-) mouse preadipocytes. Our results demonstrate that this chimeric receptor is capable of inducing apoptosis by transmembrane- as well as soluble-TNF stimuli. Moreover, we found that our bioassay based on cell death phenotype had an approximately 80-fold higher sensitivity over existing bioassays. We believe our assay system will be an invaluable research tool for studying TNFR2 and for screening TNFR2-targeted drugs.
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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/Anti-Inflammatory Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD95,
http://linkedlifedata.com/resource/pubmed/chemical/Fadd protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Fas protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Fas-Associated Death Domain Protein,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Tumor Necrosis Factor...,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Tumor Necrosis Factor...,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/TNFRSF1B protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Tnfrsf1a protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
0022-1759
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pubmed:author |
pubmed-author:AbeYasuhiroY,
pubmed-author:KamadaHaruhikoH,
pubmed-author:KatayamaKazufumiK,
pubmed-author:KayamuroHiroyukiH,
pubmed-author:MinowaKyokoK,
pubmed-author:MiyoshiHiroyukiH,
pubmed-author:MukaiYoheiY,
pubmed-author:NakagawaShinsakuS,
pubmed-author:NomuraTetsuyaT,
pubmed-author:ShibataHirokoH,
pubmed-author:TsunodaShin-IchiS,
pubmed-author:TsutsumiYasuoY,
pubmed-author:YoshikawaTomoakiT,
pubmed-author:YoshiokaYasuoY
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pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
335
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
71-8
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pubmed:meshHeading |
pubmed-meshheading:18417150-Adipocytes,
pubmed-meshheading:18417150-Animals,
pubmed-meshheading:18417150-Anti-Inflammatory Agents,
pubmed-meshheading:18417150-Antigens, CD95,
pubmed-meshheading:18417150-Apoptosis,
pubmed-meshheading:18417150-Biological Assay,
pubmed-meshheading:18417150-Cell Membrane,
pubmed-meshheading:18417150-Cell Survival,
pubmed-meshheading:18417150-Cells, Cultured,
pubmed-meshheading:18417150-Drug Evaluation, Preclinical,
pubmed-meshheading:18417150-Fas-Associated Death Domain Protein,
pubmed-meshheading:18417150-Genetic Vectors,
pubmed-meshheading:18417150-Humans,
pubmed-meshheading:18417150-Lentivirus,
pubmed-meshheading:18417150-Mice,
pubmed-meshheading:18417150-Protein Structure, Tertiary,
pubmed-meshheading:18417150-Receptors, Tumor Necrosis Factor, Type I,
pubmed-meshheading:18417150-Receptors, Tumor Necrosis Factor, Type II,
pubmed-meshheading:18417150-Recombinant Fusion Proteins,
pubmed-meshheading:18417150-Transfection,
pubmed-meshheading:18417150-Tumor Necrosis Factor-alpha
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pubmed:year |
2008
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pubmed:articleTitle |
Simple and highly sensitive assay system for TNFR2-mediated soluble- and transmembrane-TNF activity.
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pubmed:affiliation |
Laboratory of Pharmaceutical Proteomics, National Institute of Biomedical Innovation, Ibaraki, Osaka, Japan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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