| First Author | Sato S | Year | 2014 |
| Journal | ScientificWorldJournal | Volume | 2014 |
| Pages | 685854 | PubMed ID | 25401152 |
| Mgi Jnum | J:278142 | Mgi Id | MGI:6355910 |
| Doi | 10.1155/2014/685854 | Citation | Sato S, et al. (2014) Direct and indirect suppression of interleukin-6 gene expression in murine macrophages by nuclear orphan receptor REV-ERBalpha. ScientificWorldJournal 2014:685854 |
| abstractText | It is now evident that many nuclear hormone receptors can modulate target gene expression. REV-ERBalpha, 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-ERBalpha plays a key role in the mediation between clockwork and inflammation. The purpose of the current study was to investigate the role of REV-ERBalpha in the regulation of interleukin-6 (il6) gene expression in murine macrophages. REV-ERBalpha agonists, or overexpression of rev-erb alpha in the murine macrophage cell line RAW264 cells, suppressed the induction of il6 mRNA following a lipopolysaccharide (LPS) endotoxin challenge. Also, rev-erb alpha overexpression decreased LPS-stimulated nuclear factor kappaB (NFkappaB) activation in RAW264 cells. We showed that REV-ERBalpha represses il6 expression not only indirectly through an NFkappaB binding motif but also directly through a REV-ERBalpha binding motif in the murine il6 promoter region. Furthermore, peritoneal macrophages from mice lacking rev-erb alpha increased il6 mRNA expression. These data suggest that REV-ERBalpha regulates the inflammatory response of macrophages through the suppression of il6 expression. REV-ERBalpha may therefore be identified as a potent anti-inflammatory receptor and be a therapeutic target receptor of inflammatory diseases. |
