Direct and indirect suppression of interleukin-6 gene expression in murine macrophages by nuclear orphan receptor REV-ERB. Academic Article uri icon


  • It is now evident that many nuclear hormone receptors can modulate target gene expression. REV-ERB, 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-ERB plays a key role in the mediation between clockwork and inflammation. The purpose of the current study was to investigate the role of REV-ERB in the regulation of interleukin-6 (il6) gene expression in murine macrophages. REV-ERB agonists, or overexpression of rev-erb in the murine macrophage cell line RAW264 cells, suppressed the induction of il6 mRNA following a lipopolysaccharide (LPS) endotoxin challenge. Also, rev-erb overexpression decreased LPS-stimulated nuclear factor B (NFB) activation in RAW264 cells. We showed that REV-ERB represses il6 expression not only indirectly through an NFB binding motif but also directly through a REV-ERB binding motif in the murine il6 promoter region. Furthermore, peritoneal macrophages from mice lacking rev-erb increased il6 mRNA expression. These data suggest that REV-ERB regulates the inflammatory response of macrophages through the suppression of il6 expression. REV-ERB may therefore be identified as a potent anti-inflammatory receptor and be a therapeutic target receptor of inflammatory diseases.

published proceedings

  • ScientificWorldJournal

author list (cited authors)

  • Sato, S., Sakurai, T., Ogasawara, J., Shirato, K., Ishibashi, Y., Oh-ishi, S., ... Kizaki, T.

citation count

  • 41

complete list of authors

  • Sato, Shogo||Sakurai, Takuya||Ogasawara, Junetsu||Shirato, Ken||Ishibashi, Yoshinaga||Oh-ishi, Shuji||Imaizumi, Kazuhiko||Haga, Shukoh||Hitomi, Yoshiaki||Izawa, Tetsuya||Ohira, Yoshinobu||Ohno, Hideki||Kizaki, Takako

publication date

  • October 2014