| RRC ID |
67878
|
| 著者 |
Sato S, Sakurai T, Ogasawara J, Shirato K, Ishibashi Y, Oh-ishi S, Imaizumi K, Haga S, Hitomi Y, Izawa T, Ohira Y, Ohno H, Kizaki T.
|
| タイトル |
Direct and indirect suppression of interleukin-6 gene expression in murine macrophages by nuclear orphan receptor REV-ERBα.
|
| ジャーナル |
ScientificWorldJournal
|
| Abstract |
It is now evident that many nuclear hormone receptors can modulate target gene expression. REV-ERBα, one of the nuclear hormone receptors with the capacity to alter clock function, is critically involved in lipid metabolism, adipogenesis, and the inflammatory response. Recent studies suggest that REV-ERBα plays a key role in the mediation between clockwork and inflammation. The purpose of the current study was to investigate the role of REV-ERBα in the regulation of interleukin-6 (il6) gene expression in murine macrophages. REV-ERBα agonists, or overexpression of rev-erb α in the murine macrophage cell line RAW264 cells, suppressed the induction of il6 mRNA following a lipopolysaccharide (LPS) endotoxin challenge. Also, rev-erb α overexpression decreased LPS-stimulated nuclear factor κB (NFκB) activation in RAW264 cells. We showed that REV-ERBα represses il6 expression not only indirectly through an NFκB binding motif but also directly through a REV-ERBα binding motif in the murine il6 promoter region. Furthermore, peritoneal macrophages from mice lacking rev-erb α increased il6 mRNA expression. These data suggest that REV-ERBα regulates the inflammatory response of macrophages through the suppression of il6 expression. REV-ERBα may therefore be identified as a potent anti-inflammatory receptor and be a therapeutic target receptor of inflammatory diseases.
|
| 巻・号 |
2014
|
| ページ |
685854
|
| 公開日 |
2014-1-1
|
| DOI |
10.1155/2014/685854
|
| PMID |
25401152
|
| PMC |
PMC4220616
|
| MeSH |
Animals
Cell Line
Gene Expression Regulation*
Interleukin-6 / antagonists & inhibitors*
Interleukin-6 / biosynthesis*
Macrophages, Peritoneal / metabolism*
Mice
Mice, Inbred C57BL
Mice, Knockout
Nuclear Receptor Subfamily 1, Group D, Member 1 / metabolism*
Promoter Regions, Genetic / physiology
Protein Binding / physiology
|
| リソース情報 |
| ヒト・動物細胞 |
RAW 264(RCB0535) |
