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-ERBplays a key role in the mediation between clockwork and inflammation. The purpose of the current study was to investigate the role of REV-ERBin the regulation ofinterleukin-6(il6) gene expression in murine macrophages. REV-ERBagonists, or overexpression ofrev-erbin the murine macrophage cell line RAW264 cells, suppressed the induction ofil6mRNA following a lipopolysaccharide (LPS) endotoxin challenge. Also,rev-erboverexpression decreased LPS-stimulated nuclear factorB (NFB) activation in RAW264 cells. We showed that REV-ERBrepressesil6expression not only indirectly through an NFB binding motif but also directly through a REV-ERBbinding motif in the murineil6promoter region. Furthermore, peritoneal macrophages from mice lackingrev-erbincreasedil6mRNA expression. These data suggest that REV-ERBregulates the inflammatory response of macrophages through the suppression ofil6expression. REV-ERBmay therefore be identified as a potent anti-inflammatory receptor and be a therapeutic target receptor of inflammatory diseases.

published proceedings

  • The Scientific World Journal

author list (cited authors)

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

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