Accelerated degradation of retinoic acid by activated microglia
Accelerated degradation of retinoic acid by activated microglia
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DOI：
10.1016/j.jneuroim.2012.11.005
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发表时间：
2013-03-15
影响因子：
3.3
通讯作者：
Gertz, Karen
中科院分区：
文献类型：
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作者：
Hellmann-Regen, Julian;Kronenberg, Golo;Gertz, Karen
在大脑中，视黄酸（RA）浓度处于严格的时空控制之下。在这里，我们表明，挑战的主要小鼠小胶质细胞与脂多糖（LPS）的结果增加释放一氧化氮（NO）和肿瘤坏死因子-α（TNF-α）。RA的共同施用减弱了小胶质细胞活化。类似地，用RA代谢抑制剂Liarozole预处理有效地减少了NO和TNF-α的释放。相反，活化的小胶质细胞显示RA降解细胞色素CYP 26 A1、CYP 26 B1、CYP 3A 4和CYP 2C的蛋白表达增加。相应地，激活的小胶质细胞对RA的抑制作用显著增加。我们的研究结果表明，RA减少小胶质细胞的激活，但也反过来说，小胶质细胞的激活状态影响RA代谢。(C)2013爱思唯尔有限公司版权所有。
In the brain, retinoic acid (RA) concentrations are under tight spatio-temporal control. Here, we show that challenge of primary mouse microglia with lipopolysaccharide (LPS) results in increased release of nitric oxide (NO) and tumor necrosis factor-alpha (TNF-alpha). Co-administration of RA attenuated microglial activation. Similarly, pretreatment with RA-metabolism inhibitor liarozole potently reduced NO and TNF-alpha release. Conversely, activated microglia showed increased protein expression of RA-degrading cytochromes CYP26A1, CYP26B1, CYP3A4 and CYP2C. Correspondingly, RA catabolism by activated microglia was significantly increased. Our results indicate that RA reduces microglial activation, but also, conversely, that the activation state of microglia influences RA metabolism. (C) 2013 Elsevier B.V. All rights reserved.