Source:http://linkedlifedata.com/resource/pubmed/id/12869625
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
2
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pubmed:dateCreated |
2003-7-18
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pubmed:abstractText |
Phenolic antioxidants inhibit the induction of inflammatory cytokines by inflammatory stimuli. Here, we analyzed the mechanism by which the antioxidants inhibit LPS-induced expression of tumor necrosis factor alpha (TNFalpha) in macrophages. Hydroquinone and tert-butyl hydroquinone, prototypes of phenolic antioxidants, block lipopolysaccharide (LPS)-induced transcription of TNFalpha and a nuclear factor (NF)-kappaB-mediated reporter gene expression, suggesting NF-kappaB as a target in the inhibition. Analyses of the NF-kappaB activation pathway revealed that the antioxidants do not inhibit LPS-induced activation of the IkappaB kinase activity, degradation of IkappaBalpha, or translocation of activated NF-kappaB into the nucleus, but they do block the formation of NF-kappaB/DNA binding complexes. In vitro experiments showed that the antioxidants do not directly interfere with DNA binding of NF-kappaB. Structure-activity analyses suggest that inhibition of NF-kappaB function involves the redox cycling property of the antioxidants. These findings implicate a redox-sensitive factor important for the binding of NF-kappaB to its DNA recognition sequence as a target molecule in the inhibition of NF-kappaB function and inflammatory cytokine expression by phenolic antioxidants.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antioxidants,
http://linkedlifedata.com/resource/pubmed/chemical/Cytokines,
http://linkedlifedata.com/resource/pubmed/chemical/DNA,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/Phenols,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0026-895X
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
64
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
211-9
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pubmed:dateRevised |
2004-11-17
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pubmed:meshHeading |
pubmed-meshheading:12869625-Animals,
pubmed-meshheading:12869625-Antioxidants,
pubmed-meshheading:12869625-Cells, Cultured,
pubmed-meshheading:12869625-Cytokines,
pubmed-meshheading:12869625-DNA,
pubmed-meshheading:12869625-Macrophages,
pubmed-meshheading:12869625-Mice,
pubmed-meshheading:12869625-NF-kappa B,
pubmed-meshheading:12869625-Oxidation-Reduction,
pubmed-meshheading:12869625-Phenols,
pubmed-meshheading:12869625-Signal Transduction,
pubmed-meshheading:12869625-Transcription, Genetic,
pubmed-meshheading:12869625-Tumor Necrosis Factor-alpha
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pubmed:year |
2003
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pubmed:articleTitle |
Inhibition of nuclear factor kappaB by phenolic antioxidants: interplay between antioxidant signaling and inflammatory cytokine expression.
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pubmed:affiliation |
Receptor Biology Laboratory, Toxicology and Molecular Biology Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health/Centers for Disease Control and Prevention, Morgantown, WV 26505, USA. qam1@cdc.gov
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pubmed:publicationType |
Journal Article
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