The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
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Regulatory Effect of 25-hydroxyvitamin $D_3$ on Nitric Oxide Production in Activated Microglia

  • Hur, Jinyoung (Korea Food Research Institute) ;
  • Lee, Pyeongjae (Department of Natural Medicine Resources, Semyung University) ;
  • Kim, Mi Jung (Department of Physiology, Biomedical Science Institute and Medical Research Center for Reactive Oxygen Species, School of Medicine, Kyung Hee University) ;
  • Cho, Young-Wuk (Department of Physiology, Biomedical Science Institute and Medical Research Center for Reactive Oxygen Species, School of Medicine, Kyung Hee University)
  • Received : 2014.05.19
  • Accepted : 2014.08.20
  • Published : 2014.10.30
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Abstract

Microglia are activated by inflammatory and pathophysiological stimuli in neurodegenerative diseases, and activated microglia induce neuronal damage by releasing cytotoxic factors like nitric oxide (NO). Activated microglia synthesize a significant amount of vitamin $D_3$ in the rat brain, and vitamin $D_3$ has an inhibitory effect on activated microglia. To investigate the possible role of vitamin $D_3$ as a negative regulator of activated microglia, we examined the effect of 25-hydroxyvitamin $D_3$ on NO production of lipopolysaccharide (LPS)-stimulated microglia. Treatment with LPS increased the production of NO in primary cultured and BV2 microglial cells. Treatment with 25-hydroxyvitamin $D_3$ inhibited the generation of NO in LPS-activated primary microglia and BV2 cells. In addition to NO production, expression of 1-${\alpha}$-hydroxylase and the vitamin D receptor (VDR) was also upregulated in LPS-stimulated primary and BV2 microglia. When BV2 cells were transfected with 1-${\alpha}$-hydroxylase siRNA or VDR siRNA, the inhibitory effect of 25-hydroxyvitamin $D_3$ on activated BV2 cells was suppressed. 25-Hydroxyvitamin $D_3$ also inhibited the increased phosphorylation of p38 seen in LPS-activated BV2 cells, and this inhibition was blocked by VDR siRNA. The present study shows that 25-hydroxyvitamin $D_3$ inhibits NO production in LPS-activated microglia through the mediation of LPS-induced 1-${\alpha}$-hydroxylase. This study also shows that the inhibitory effect of 25-hydroxyvitamin $D_3$ on NO production might be exerted by inhibiting LPS-induced phosphorylation of p38 through the mediation of VDR signaling. These results suggest that vitamin $D_3$ might have an important role in the negative regulation of microglial activation.

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References

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