Stimulation of nuclear receptor REV-ERBs regulates tumor necrosis factor-induced expression of proinflammatory molecules in C6 astroglial cells

Stimulation of rat C6 astroglial cells with tumor necrosis factor (10 ng/ml) significantly increased the mRNA expression of CCL2, IL-6, iNOS, and MMP-9.

• Activated astrocytes produce neurotoxic molecules following inflammation and injury in the central nervous system.
• REV-ERBs may play a role in regulating the expression of inflammatory molecules in astrocytes.
• Treatment with REV-ERB agonists significantly blocked TNF-induced upregulation of CCL2 and MMP-9 mRNA.
• The selective HDAC3 inhibitor RGFP966 reversed the inhibitory effects of a REV-ERB agonist on MMP-9 expression.
• REV-ERB activation is associated with downregulation of MMP-9 and CCL2 transcription via different mechanisms.

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