期刊
NEUROCHEMICAL RESEARCH
卷 41, 期 11, 页码 2848-2858出版社
SPRINGER/PLENUM PUBLISHERS
DOI: 10.1007/s11064-016-2000-3
关键词
Lipopolysaccharide; Retinoid X receptor; Extracellular signal-regulated kinase; Nuclear factor kappa B; Inducible nitric oxide synthase; Interleukin-6
资金
- JSPS KAKENHI [26670036, 16H04673, 16K15204]
- Program for Leading Graduate Schools HIGO (Health life science: Interdisciplinary and Glocal Oriented), MEXT, Japan
- Grants-in-Aid for Scientific Research [15K18865, 26670036, 16H04673, 16K08276, 16K15204] Funding Source: KAKEN
Inhibition of pro-inflammatory functions of microglia has been considered a promising strategy to prevent pathogenic events in the central nervous system under neurodegenerative conditions. Here we examined potential inhibitory effects of nuclear receptor ligands on lipopolysaccharide (LPS)-induced inflammatory responses in microglial BV-2 cells. We demonstrate that a vitamin D receptor agonist 1,25-dihydroxyvitamin D-3 (VD3) and a retinoid X receptor agonist HX630 affect LPS-induced expression of pro-inflammatory factors. Specifically, both VD3 and HX630 inhibited expression of mRNAs encoding inducible nitric oxide synthase (iNOS) and IL-6, whereas expression of IL-1 beta mRNA was inhibited only by VD3. The inhibitory effect of VD3 and HX630 on expression of iNOS and IL-6 mRNAs was additive. Effect of VD3 and HX630 was also observed for inhibition of iNOS protein expression and nitric oxide production. Moreover, VD3 and HX630 inhibited LPS-induced activation of extracellular signal-regulated kinase (ERK) and nuclear translocation of nuclear factor kappa B (NF-kappa B). PD98059, an inhibitor of ERK kinase, attenuated LPS-induced nuclear translocation of NF-kappa B and induction of mRNAs for iNOS, IL-1 beta and IL-6. These results indicate that VD3 can inhibit production of several pro-inflammatory molecules from microglia, and that suppression of ERK activation is at least in part involved in the anti-inflammatory effect of VD3.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据