| RRC ID |
10827
|
| 著者 |
Yoshida H, Kwon AH, Habara K, Yamada M, Kaibori M, Kamiyama Y, Nishizawa M, Ito S, Okumura T.
|
| タイトル |
Edaravone inhibits the induction of iNOS gene expression at transcriptional and posttranscriptional steps in murine macrophages.
|
| ジャーナル |
Shock
|
| Abstract |
Edaravone, a free radical scavenger, plays crucial roles in the prevention of injuries to the brain, heart, and liver. Our in vivo study indicated that edaravone prevented endotoxin-induced liver injury through inhibition of NO production in addition to reductions in oxidative products and proinflammatory cytokine induction. Studies were performed to determine whether edaravone directly influences the induction of iNOS in murine RAW264 macrophages as a substitute for Kupffer cells (resident macrophages) in the liver. RAW264 cells were treated with LPS (1 microg/mL) in the presence or absence of edaravone. NO production, iNOS induction, and its related signaling were analyzed. Edaravone (0.5 - 5 mM) decreased the production of NO stimulated by LPS in time- and dose-dependent manners, and these concentrations of edaravone had no cytotoxic effects. Edaravone decreased the levels of iNOS protein and mRNA. Transfection experiments with iNOS promoter-luciferase constructs revealed that edaravone inhibited the activities of both iNOS promoter transactivation and iNOS mRNA stabilization. However, edaravone did not have any effects on I kappaB alpha degradation or nuclear factor-kappaB activation. In contrast, edaravone markedly suppressed the LPS-stimulated expression of iNOS antisense-transcript, which stabilizes iNOS mRNA by interacting with its 3'-untranslated region and RNA-binding proteins. Edaravone may inhibit the induction of iNOS gene expression at the steps of its promoter transactivation in a nuclear factor-kappaB-independent manner and mRNA stabilization in RAW264 cells.
|
| 巻・号 |
30(6)
|
| ページ |
734-9
|
| 公開日 |
2008-12-1
|
| DOI |
10.1097/SHK.0b013e318173ea0b
|
| PMID |
18496239
|
| MeSH |
Animals
Antipyrine / analogs & derivatives*
Antipyrine / pharmacology
Blotting, Northern
Blotting, Western
Cell Line
Edaravone
Free Radical Scavengers / pharmacology*
Gene Expression / drug effects
Gene Expression / genetics
Macrophages / drug effects*
Macrophages / metabolism*
Mice
NF-kappa B
Nitric Oxide / metabolism
Nitric Oxide Synthase Type II / genetics*
Nitric Oxide Synthase Type II / metabolism*
Promoter Regions, Genetic / drug effects
Promoter Regions, Genetic / genetics
RNA Stability / drug effects
RNA, Messenger / genetics
Transcription, Genetic / drug effects
Transcription, Genetic / genetics
|
| IF |
2.96
|
| 引用数 |
15
|
|
WOS 分野
|
SURGERY
CRITICAL CARE MEDICINE
HEMATOLOGY
PERIPHERAL VASCULAR DISEASE
|
| リソース情報 |
| ヒト・動物細胞 |
RAW 264(RCB0535) |
