The orphan nuclear receptor REV-ERBs exert as transcriptional regulatory factors, and have functions in the regulation of circadian rhythm, inflammation and metabolism. Microglia are crucial in inflammatory responses such as production of pro-inflammatory molecules in the CNS, and involved in the development of various neurodegenerative diseases. However, the role of microglial REV-ERBs in inflammatory responses has yet to be elucidated.
Primary microglia were prepared from cerebral cortices of neonatal Wistar rats. Expression levels of mRNA or protein were examined by real-time PCR or western-blotting, respectively.
Treatment of cultured microglia with specific REV-ERBs agonist SR9009 prevented the lipopolysaccharide (LPS)-induced mRNA expression of pro-inflammatory cytokines interleukin-1β, interleukin-6 and tumor necrosis factor. Furthermore, treatment with SR9009 inhibited LPS-induced phosphorylation of p38 and p65 subunit of NF-kB.
The current study suggests that REV-ERBs contribute to the regulation of expression of pro-inflammatory molecules through the inhibition of p38 and NF-kB in cultured cortical microglia.