Gng12 is a novel negative regulator of LPS-induced inflammation in the microglial cell line BV-2
Gng12 is a novel negative regulator of LPS-induced inflammation in the microglial cell line BV-2
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DOI：
10.1007/s00011-009-0062-2
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发表时间：
2010-01-01
影响因子：
6.7
通讯作者：
Dabrowski, Michal
中科院分区：
文献类型：
--
作者：
Larson, Kelley C.;Draper, Michael P.;Dabrowski, Michal
炎症在许多神经退行性疾病中起着核心作用，包括帕金森氏症、阿尔茨海默氏症、多发性硬化症、肌萎缩侧索硬化症和艾滋病痴呆。小胶质细胞是中枢神经系统的常驻巨噬细胞，并且是主要负责这些疾病的炎症组分的细胞。我们比较了LPS刺激后神经特异性小胶质细胞系BV-2和巨噬细胞系BV-2的特征，鉴定了在LPS刺激后仅在小胶质细胞中调节的一组77个基因。进一步研究了一个感兴趣的基因Gng 12，以确定其改变炎症反应的能力。具体而言，LPS刺激后Gng 12 mRNA水平瞬时增加。此外，LPS刺激后BV-2细胞中Gng 12 mRNA的总体水平显著高于巨噬细胞。使用RNAi调节Gng 12 mRNA水平揭示了该因子在基于对亚硝酸盐和TNF α水平的影响的总体炎症反应的负调节中的新作用。这些数据表明，Gng 12是LPS反应的负调节因子，可能是整个炎症信号级联反应中的重要因素。
Inflammation plays a central role in many neurodegenerative diseases, including Parkinson's, Alzheimer's, multiple sclerosis, amyotrophic lateral sclerosis, and AIDS dementia. Microglia are the resident macrophages of the central nervous system and are the cells primarily responsible for the inflammatory component of these diseases.Using gene expression profiling, we compared the profile of the neurospecific microglial cell line BV-2 after LPS stimulation to that of a macrophage cell line (J774A.1) stimulated with LPS.A set of 77 genes that were modulated only in microglial cells after LPS stimulation was identified. One gene of interest, Gng12, was investigated further to determine its ability to modify the inflammatory response. Specifically, Gng12 mRNA levels were transiently increased after LPS stimulation. In addition, overall levels of Gng12 mRNA after LPS stimulation were significantly higher in BV-2 cells as compared to macrophage cells.Modulating Gng12 mRNA levels using RNAi revealed a novel role for the factor in the negative regulation of the overall inflammatory response as based on effects on nitrite and TNF alpha levels. These data suggest that Gng12 is a negative regulator of the LPS response and may be an important factor in the overall inflammatory signaling cascade.