Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2005-7-15
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
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
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0006-2952
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
70
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
618-26
pubmed:dateRevised
2009-11-19
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
pubmed:year
2005
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.
pubmed:affiliation
Department of Education and Research, Taichung Veterans General Hospital, #160 Sec. 3 Chung Kang Road, Taichung 407, Taiwan, ROC.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't