Regulatory Effect of 25-hydroxyvitamin D3 on Nitric Oxide Production in Activated Microglia

• 영문명: Regulatory Effect of 25-hydroxyvitamin D₃ on Nitric Oxide Production in Activated Microglia
• 발행기관: 대한생리학회-대한약리학회
• 저자명: Jinyoung Hur Pyeongjae Lee Mi Jung Kim Young-Wuk Cho
• 간행물 정보: 『The Korean Journal of Physiology & Pharmacology』제18권 제5호, 397~402쪽, 전체 6쪽
• 주제분류: 의약학 > 의학일반
• 파일형태: PDF
• 발행일자: 2014.01.01

영문 초록

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.

키워드

25-Hydroxyvitamin D₃ 1-α-Hydroxylase Microglia activation Vitamin D receptor