Vitamin D-2 suppresses amyloid-beta 25-35 induced microglial activation in BV2 cells by blocking the NF-kappa B inflammatory signaling pathway

作者：Raha Suchismita; Lee Ho Jeong; Yumnam Silvia; Hong Gyeong Eun; Saralamma Venu Venkatarame Gowda; Ha Yeong Lae; Kim Jeong Ok; Kim Young Suk; Heo Jeong Doo; Lee Sang Joon; Kim Eun Hee; Kim Gon Sup

来源：Life Sciences, 2016, 161: 37-44.

DOI：10.1016/j.lfs.2016.07.017

• Alzheimer
• Amyloid-beta 25-35
• Vitamin D-2
• Nuclear factor-kappaB
• BV2 microglial cells
• Inflammation

Aims: Present emerging world is emphasizing the implication of vitamin D deficiency associated with development of inflammation and neurodegenerative disorder like Alzheimer's disease (AD). The chief neuropathological hallmark of AD is aggregation of amyloid-beta (A beta) peptides surrounding microglial cells in human brain. Microglial activation plays a key role in inflammatory response and neuronal injury. Naturally abundant vitamin D-2 (VD2) exhibiting anti-inflammatory activities are yet to explore more. This study has investigated the inhibitory effect of VD2 on inflammatory activities of BV2 microglial cells.
Main methods: Cellular compatibility of VD2 and A beta 25-35 protein in treated BV2 microglial cells were measured by CCK-8 assay. Induction of iNOS, COX-2 and NF-kappa B signaling cascade were measured by western blotting, whereas pro-inflammatory cytokines were measured by ELISA. In addition, generation of ROS was detected by fluorescence intensity.
Key findings: Morphological observations showed that A beta 25-35 induced BV2 cells stimulation noticeably got reduced in VD2 pre-treated group at 24 h time period. Anti-inflammatory activities of VD2 was observed demonstrating the inhibition of up-regulated iNOS and COX-2 protein expression further confirmed by attenuating the activated microglia released pro-inflammatory cytokines IL-1 beta, IL-6, TNF-alpha and ROS, while blocking the phosphorylation of NF-kappa B p65 in nucleus by preventing I kappa B-alpha degradation and phosphorylation in cytosol.
Significance: The present study revealed that VD2 blocked the phosphorylation of NF-kappa B inflammatory signaling pathway in A beta 25-35 induced activated BV2 microglial cells by suppressing ROS generation and inflammatory cytokines. Our finding suggests that vitamin D-2 has therapeutic potential against inflammation and Alzheimer's disease.

• 出版日期2016-9-15