Linked Life Data

17936043

Source:http://linkedlifedata.com/resource/pubmed/id/17936043

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2007-12-31
pubmed:abstractText
Nitric oxide (NO) generated from inducible NO synthase (iNOS) during hepatic injury has been reported to contribute to cytoprotection or cellular damage. Rebamipide, anti-gastric ulcer drug, has protective effects in a variety of tissue and organ injury. However, it remains unknown whether rebamipide is involved in the regulation of iNOS gene expression under pathological conditions. We examined whether rebamipide influences the induction of iNOS in hepatocytes exposed to pro-inflammatory cytokine. Primary cultured rat hepatocytes were treated with interleukin (IL)-1beta in the presence or absence of rebamipide. Pretreatment of cells with rebamipide resulted in up-regulation of iNOS induction by IL-1beta, followed by increased NO production. Rebamipide enhanced the degradation of IkappaBalpha and the activation of NF-kappaB. Further, rebamipide super-induced the up-regulation of type I IL-1 receptor (IL-1RI), which is essential for iNOS induction in addition to the IkappaB/NF-kappaB pathway. Transfection experiments revealed that rebamipide increased the transactivation of iNOS promoter and the stability of iNOS mRNA. In the latter, rebamipide increased the antisense-transcript corresponding to the 3'-UTR of iNOS mRNA, which stabilizes iNOS mRNA by interacting with the 3'-UTR and RNA-binding proteins. These findings demonstrate that rebamipide up-regulates iNOS by iNOS promoter activation through NF-kappaB, and by its mRNA stabilization presumably through the super-induction of IL-1RI and antisense-transcript. Rebamipide may contribute to a novel potentiated treatment in liver injuries.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1089-8603
pubmed:author
pubmed:issnType
Print
pubmed:volume
18
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
28-36
pubmed:meshHeading
pubmed-meshheading:17936043-Alanine, pubmed-meshheading:17936043-Animals, pubmed-meshheading:17936043-Anti-Ulcer Agents, pubmed-meshheading:17936043-Cells, Cultured, pubmed-meshheading:17936043-Enzyme Induction, pubmed-meshheading:17936043-Hepatocytes, pubmed-meshheading:17936043-Humans, pubmed-meshheading:17936043-I-kappa B Proteins, pubmed-meshheading:17936043-Interleukin-1beta, pubmed-meshheading:17936043-Male, pubmed-meshheading:17936043-Nitric Oxide, pubmed-meshheading:17936043-Nitric Oxide Synthase Type II, pubmed-meshheading:17936043-Phosphorylation, pubmed-meshheading:17936043-Quinolones, pubmed-meshheading:17936043-Rats, pubmed-meshheading:17936043-Rats, Wistar, pubmed-meshheading:17936043-Receptors, Interleukin-1 Type I, pubmed-meshheading:17936043-Recombinant Proteins, pubmed-meshheading:17936043-Signal Transduction, pubmed-meshheading:17936043-Time Factors, pubmed-meshheading:17936043-Up-Regulation
pubmed:year
2008
pubmed:articleTitle
Rebamipide, anti-gastric ulcer drug, up-regulates the induction of iNOS in proinflammatory cytokine-stimulated hepatocytes.
pubmed:affiliation
The Department of Surgery, Kansai Medical University, Moriguchi, Osaka 570-8506, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't