Source:http://linkedlifedata.com/resource/pubmed/id/15998510
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
4
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pubmed:dateCreated |
2005-7-15
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pubmed:abstractText |
The large amount of nitric oxide (NO) produced by inducible NO synthase (iNOS) contributes to cellular injury in inflammatory disease. In the present study, a novel synthetic compound (3E)-4-(2-hydroxyphenyl)but-3-en-2-one (HPB) was found to inhibit lipopolysaccharide (LPS)-induced NO generation, but not through the inhibition of iNOS activity, in RAW 264.7 macrophages. Administration of HPB into mice also inhibited the LPS-induced increase in serum nitrite/nitrate levels. To evaluate the underlying mechanisms of HPB inhibition of NO generation, the expression of the iNOS gene in RAW 264.7 macrophages was examined. HPB abolished the LPS-induced expression of iNOS protein, iNOS mRNA and iNOS promoter activity in a similar concentration-dependent manner. LPS-induced nuclear factor-kappaB (NF-kappaB) DNA binding and NF-kappaB-dependent reporter gene activity were both significantly inhibited by HPB. This effect was mediated through the inhibition of inhibitory factor-kappaBalpha (IkappaBalpha) phosphorylation and degradation, and of p65 nuclear translocation. HPB had no effect on the LPS-induced phosphorylation of extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinases (MAPK), and c-Jun NH(2)-terminal kinase (JNK). However, HPB suppressed the LPS-induced intracellular reactive oxygen species (ROS) production. These results indicate that HPB down-regulates iNOS gene expression probably through the inhibition of LPS-induced intracellular ROS production, which has been implicated in the activation of NF-kappaB.
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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/Butanones,
http://linkedlifedata.com/resource/pubmed/chemical/DNA,
http://linkedlifedata.com/resource/pubmed/chemical/DNA Primers,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Lipopolysaccharides,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide Synthase,
http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide Synthase Type II,
http://linkedlifedata.com/resource/pubmed/chemical/Nos2 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Phenols,
http://linkedlifedata.com/resource/pubmed/chemical/Reactive Oxygen Species
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0006-2952
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
70
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
618-26
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:15998510-Animals,
pubmed-meshheading:15998510-Base Sequence,
pubmed-meshheading:15998510-Butanones,
pubmed-meshheading:15998510-Cell Line,
pubmed-meshheading:15998510-DNA,
pubmed-meshheading:15998510-DNA Primers,
pubmed-meshheading:15998510-Electrophoretic Mobility Shift Assay,
pubmed-meshheading:15998510-Enzyme Activation,
pubmed-meshheading:15998510-Enzyme Inhibitors,
pubmed-meshheading:15998510-Lipopolysaccharides,
pubmed-meshheading:15998510-Mice,
pubmed-meshheading:15998510-Mice, Inbred BALB C,
pubmed-meshheading:15998510-Mitogen-Activated Protein Kinases,
pubmed-meshheading:15998510-NF-kappa B,
pubmed-meshheading:15998510-Nitric Oxide Synthase,
pubmed-meshheading:15998510-Nitric Oxide Synthase Type II,
pubmed-meshheading:15998510-Phenols,
pubmed-meshheading:15998510-Reactive Oxygen Species
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pubmed:year |
2005
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pubmed:articleTitle |
Inhibition of lipopolysaccharide-induced expression of inducible nitric oxide synthase by phenolic (3E)-4-(2-hydroxyphenyl)but-3-en-2-one in RAW 264.7 macrophages.
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pubmed:affiliation |
Department of Education and Research, Taichung Veterans General Hospital, #160 Sec. 3 Chung Kang Road, Taichung 407, Taiwan, ROC.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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