Direct and indirect suppression of interleukin-6 gene expression in murine macrophages by nuclear orphan receptor REV-ERB α

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

    Research output: Contribution to journalArticle

    24 Citations (Scopus)

    Abstract

    It is now evident that many nuclear hormone receptors can modulate target gene expression. REV-ERB α, 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 α 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 α in the regulation of interleukin-6 (il6) gene expression in murine macrophages. REV-ERB α 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 B (NFB) activation in RAW264 cells. We showed that REV-ERB α represses il6 expression not only indirectly through an NFB binding motif but also directly through a REV-ERB α 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-ERB α regulates the inflammatory response of macrophages through the suppression of il6 expression. REV-ERB α may therefore be identified as a potent anti-inflammatory receptor and be a therapeutic target receptor of inflammatory diseases.

    Original languageEnglish
    Article number685854
    JournalScientific World Journal
    Volume2014
    DOIs
    Publication statusPublished - 2014

    Fingerprint

    Orphan Nuclear Receptors
    orphan
    Macrophages
    Gene expression
    gene expression
    hormone
    Interleukin-6
    Gene Expression
    metabolism
    lipid
    Cytoplasmic and Nuclear Receptors
    Lipopolysaccharides
    Adipogenesis
    Messenger RNA
    Peritoneal Macrophages
    Lipid Metabolism
    Genetic Promoter Regions
    Endotoxins
    Clocks
    Anti-Inflammatory Agents

    ASJC Scopus subject areas

    • Biochemistry, Genetics and Molecular Biology(all)
    • Environmental Science(all)
    • Medicine(all)

    Cite this

    Sato, S., Sakurai, T., Ogasawara, J., Shirato, K., Ishibashi, Y., Oh-Ishi, S., ... Kizaki, T. (2014). Direct and indirect suppression of interleukin-6 gene expression in murine macrophages by nuclear orphan receptor REV-ERB α. Scientific World Journal, 2014, [685854]. https://doi.org/10.1155/2014/685854

    Direct and indirect suppression of interleukin-6 gene expression in murine macrophages by nuclear orphan receptor REV-ERB α. / 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.

    In: Scientific World Journal, Vol. 2014, 685854, 2014.

    Research output: Contribution to journalArticle

    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 2014, 'Direct and indirect suppression of interleukin-6 gene expression in murine macrophages by nuclear orphan receptor REV-ERB α', Scientific World Journal, vol. 2014, 685854. https://doi.org/10.1155/2014/685854
    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. / Direct and indirect suppression of interleukin-6 gene expression in murine macrophages by nuclear orphan receptor REV-ERB α. In: Scientific World Journal. 2014 ; Vol. 2014.
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