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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
12
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pubmed:dateCreated |
1994-7-13
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pubmed:abstractText |
TNF-alpha is a multifunctional cytokine that has been shown to activate a number of intracellular second messenger pathways. Recent studies demonstrate that the sphingomyelinase-ceramide pathway plays a potential role in the activation of nuclear factor-kappa B (NF-kappa B) by TNF-alpha. The following experiments both confirm that the addition of ceramide to cells can activate NF-kappa B and demonstrate that a 48-h pretreatment with phorbol 12-myristate (PMA) results in the loss of the ceramide-induced NF-kappa B response. In parallel experiments, in which SW480 cells were pretreated with PMA, TNF-alpha provided a signal resulting in the nuclear translocation of NF-kappa B that was similar to untreated cells. These data combined suggest that additional pathways exist that TNF-alpha can use for the activation of NF-kappa B. Supplementary data demonstrates that TNF-alpha, ceramide, and PMA activate a human cytomegalovirus-(HCMV) beta gal construct (promoter is responsive to NF-kappa B) that was stably transfected into the TNF receptor-bearing tumor cell line, SW480. PMA pretreatment of these cells resulted in a significant decrease in both the PMA and ceramide generated responses, 6% and 0% of controls, respectively. However, the response generated by TNF-alpha was not inhibited significantly (96% of control cells). This data suggests that although ceramide and 1,2-diacylglycerol (DAG) pathways may contribute to TNF-alpha activation of NF-kappa B, impedance of these pathways does not block TNF-alpha from activating NF-kappa B nor induction of the functional activation of the NF-kappa B responsive reporter construct, HCMV.
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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/Ceramides,
http://linkedlifedata.com/resource/pubmed/chemical/DNA,
http://linkedlifedata.com/resource/pubmed/chemical/Diglycerides,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase C,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-jun,
http://linkedlifedata.com/resource/pubmed/chemical/Sphingomyelin Phosphodiesterase,
http://linkedlifedata.com/resource/pubmed/chemical/Tetradecanoylphorbol Acetate,
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 |
0022-1767
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
152
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
5877-82
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pubmed:dateRevised |
2007-11-15
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pubmed:meshHeading |
pubmed-meshheading:8207213-Animals,
pubmed-meshheading:8207213-Base Sequence,
pubmed-meshheading:8207213-Binding Sites,
pubmed-meshheading:8207213-Cell Line,
pubmed-meshheading:8207213-Ceramides,
pubmed-meshheading:8207213-Consensus Sequence,
pubmed-meshheading:8207213-Cytomegalovirus,
pubmed-meshheading:8207213-DNA,
pubmed-meshheading:8207213-Diglycerides,
pubmed-meshheading:8207213-Humans,
pubmed-meshheading:8207213-Molecular Sequence Data,
pubmed-meshheading:8207213-NF-kappa B,
pubmed-meshheading:8207213-Protein Binding,
pubmed-meshheading:8207213-Protein Kinase C,
pubmed-meshheading:8207213-Proto-Oncogene Proteins c-jun,
pubmed-meshheading:8207213-Sphingomyelin Phosphodiesterase,
pubmed-meshheading:8207213-Tetradecanoylphorbol Acetate,
pubmed-meshheading:8207213-Tumor Necrosis Factor-alpha
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pubmed:year |
1994
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pubmed:articleTitle |
Inhibition of ceramide pathway does not affect ability of TNF-alpha to activate nuclear factor-kappa B.
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pubmed:affiliation |
Institute for Inflammation and Experimental Medicine, Miles Research Center, West Haven, CT 06516.
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pubmed:publicationType |
Journal Article
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