Regulatory Effect of 25-hydroxyvitamin D3 on Nitric Oxide Production in Activated Microglia.
10.4196/kjpp.2014.18.5.397
- Author:
Jinyoung HUR
1
;
Pyeongjae LEE
;
Mi Jung KIM
;
Young Wuk CHO
Author Information
1. Korea Food Research Institute, Seongnam 463-746, Korea.
- Publication Type:Original Article
- Keywords:
25-Hydroxyvitamin D3;
1-alpha-Hydroxylase;
Microglia activation;
Vitamin D receptor
- MeSH:
Animals;
Brain;
Calcifediol*;
Cholecalciferol;
Microglia*;
Negotiating;
Neurodegenerative Diseases;
Neurons;
Nitric Oxide*;
Phosphorylation;
Rats;
Receptors, Calcitriol;
RNA, Small Interfering
- From:The Korean Journal of Physiology and Pharmacology
2014;18(5):397-402
- CountryRepublic of Korea
- Language:English
-
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-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 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-alpha-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.
