|
KMID : 0811720140180050397
|
|
Korean Journal of Physiology & Pharmacology
2014 Volume.18 No. 5 p.397 ~ p.402
|
|
|
Regulatory Effect of 25-hydroxyvitamin D3 on Nitric Oxide Production in Activated Microglia
|
|
Hur Jin-Young
Lee Pyeong-Jae
Kim Mi-Jung
Cho Young-Wuk
|
|
|
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 D3 in the rat brain, and vitamin D3 has an inhibitory effect on activated microglia. To investigate the possible role of vitamin D3 as a negative regulator of activated microglia, we examined the effect of 25-hydroxyvitamin D3 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 D3 inhibited the generation of NO in LPS-activated primary microglia and BV2 cells. In addition to NO production, expression of 1-α-hydroxylase and the vitamin D receptor (VDR) was also upregulated in LPS-stimulated primary and BV2 microglia. When BV2 cells were transfected with 1-α-hydroxylase siRNA or VDR siRNA, the inhibitory effect of 25-hydroxyvitamin D3 on activated BV2 cells was suppressed. 25-Hydroxyvitamin D3 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 D3 inhibits NO production in LPS-activated microglia through the mediation of LPS-induced 1-α-hydroxylase. This study also shows that the inhibitory effect of 25-hydroxyvitamin D3 on NO production might be exerted by inhibiting LPS-induced phosphorylation of p38 through the mediation of VDR signaling. These results suggest that vitamin D3 might have an important role in the negative regulation of microglial activation.
|
|
|
KEYWORD
|
|
|
25-Hydroxyvitamin D3, 1-α-Hydroxylase, Microglia activation, Vitamin D receptor
|
|
|
FullTexts / Linksout information
|
|
|
|
|
Listed journal information
|
|
  
|