It is now evident that many nuclear hormone receptors can modulate target gene expression. REV-ERB????, one of the nuclear\nhormone receptors with the capacity to alter clock function, is critically involved in lipid metabolism, adipogenesis, and the\ninflammatory response. Recent studies suggest that REV-ERB???? plays a key role in the mediation between clockwork and\ninflammation. The purpose of the current study was to investigate the role of REV-ERB???? in the regulation of interleukin-6 (il6)\ngene expression in murine macrophages. REV-ERB???? agonists, or over expression of rev-erb???? in the murine macrophage cell line\nRAW264 cells, suppressed the induction of il6 mRNA following a lipopolysaccharide (LPS) endotoxin challenge. Also, rev-erb????\nover expression decreased LPS-stimulated nuclear factor ????B (NF????B) activation in RAW264 cells. We showed that REV-ERB????\nrepresses il6 expression not only indirectly through an NF????B bindingmotif but also directly through a REV-ERB???? bindingmotif in\nthe murine il6 promoter region. Furthermore, peritonealmacrophages frommice lacking rev-erb???? increased il6 mRNA expression.\nThese data suggest that REV-ERB???? regulates the inflammatory response of macrophages through the suppression of il6 expression.\nREV-ERB???? may therefore be identified as a potent anti-inflammatory receptor and be a therapeutic target receptor of inflammatory\ndiseases.
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