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Inhibitory mechanism of MMP-9 gene expression by ethyl pyruvate in lipopolysaccharide-stimulated BV2 microglial cells
- Title
- Inhibitory mechanism of MMP-9 gene expression by ethyl pyruvate in lipopolysaccharide-stimulated BV2 microglial cells
- Authors
- Lee E.-J.; Kim H.-S.
- Ewha Authors
- 김희선
- SCOPUS Author ID
- 김희선
- Issue Date
- 2011
- Journal Title
- Neuroscience Letters
- ISSN
- 0304-3940
- Citation
- Neuroscience Letters vol. 493, no. 41276, pp. 38 - 43
- Indexed
- SCI; SCIE; SCOPUS
- Document Type
- Article
- 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. © 2011 Elsevier Ireland Ltd.
- DOI
- 10.1016/j.neulet.2011.02.016
- Appears in Collections:
- 의과대학 > 의학과 > Journal papers
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