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

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