期刊
EXPERIMENTAL AND MOLECULAR MEDICINE
卷 44, 期 6, 页码 369-377出版社
SPRINGERNATURE
DOI: 10.3858/emm.2012.44.6.042
关键词
chalcone; lipopolysaccharides; microglia; NF-kappa B; proto-oncogene proteins c-akt; Toll-like receptor 4
资金
- Korea Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea [A101915]
- Korea Health Promotion Institute [A101915] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Microglial cells are the resident innate immune cells that sense pathogens and tissue injury in the central nervous system (CNS). Microglial activation is critical for neuroinflammatory responses. The synthetic compound 2-hydroxy-3',5,5'-trimethoxychalcone (DK-139) is a novel chalcone-derived compound. In this study, we investigated the effects of DK-139 on Toll-like receptor 4 (TLR4)-mediated inflammatory responses in BV2 microglial cells. DK-139 inhibited lipopolysaccharide (LPS)-induced TLR4 activity, as determined using a cell-based assay. DK-139 blocked LPS-induced phosphorylation of I kappa B and p65/RelA NF-kappa B, resulting in inhibition of the nuclear translocation and trans-acting activity of NF-kappa B in BV2 microglial cells. We also found that DK-139 reduced the expression of NF-kappa B target genes, such as those for COX-2, iNOS, and IL-10, in LPS-stimulated BV2 microglial cells. Interestingly, DK-139 blocked LPS-induced Akt phosphorylation. Inhibition of Akt abrogated LPS-induced phosphorylation of p65/RelA, while overexpression of dominant-active p110CAAX enhanced p65/RelA phosphorylation as well as iNOS and COX2 expression. These results suggest that DK-139 exerts an anti-inflammatory effect on microglial cells by inhibiting the Akt/I kappa B kinase (IKK)/NF-kappa B signaling pathway.
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