Inhibitory mechanism of MMP-9 gene expression by ethyl pyruvate in lipopolysaccharide-stimulated BV2 microglial cells

Eun Jung Lee, Hee Sun Kim

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

Ethyl pyruvate (EP) is a stable derivative of pyruvate and has been identified as a therapeutic agent for various inflammatory diseases. In the present study, we showed that EP and sodium pyruvate (SP) inhibited the production of TNF-α, nitric oxide (NO), or reactive oxygen species (ROS) in LPS-stimulated BV2 microglial cells. The inhibitory effects of EP were more potent than SP. Because matrix metalloproteinase-9 (MMP-9) plays a key role in neuroinflammation, as well as in neuronal cell death, we examined the effect of EP on MMP-9 expression. RT-PCR and Western blot analyses revealed that EP inhibits MMP-9 expression at mRNA and protein levels in LPS-stimulated BV2 cells. In addition, EP suppressed MMP-9 secretion, as demonstrated by gelatin zymography analysis. In contrast, SP did not affect MMP-9 expression at an equivalent concentration of EP. Further mechanistic studies revealed that EP inhibits MMP-9 promoter activity by reducing the binding of NF-κB and AP-1 to its cognitive binding sites. In addition, EP suppressed LPS-induced phosphorylation of p38 MAPK, ERK, and Akt, which are upstream signaling molecules in MMP-9 gene expression. Taken together, our data suggest that the inhibition of MMP-9 may be one of the factors contributing to anti-inflammatory activity of EP in LPS-stimulated microglia.

Original languageEnglish
Pages (from-to)38-43
Number of pages6
JournalNeuroscience Letters
Volume493
Issue number1-2
DOIs
StatePublished - 8 Apr 2011

Keywords

  • Ethyl pyruvate
  • Gene regulation
  • Inflammation
  • Microglia
  • MMP-9

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