Department of Neurology, The First Affiliated School of Harbin Medical University, Harbin 150001, China.
Department of Neurology, Heilongjiang Provincial Hospital, Harbin 150036, China.
Biochem Biophys Res Commun. 2014 Sep 26;452(3):450-6. doi: 10.1016/j.bbrc.2014.08.092. Epub 2014 Aug 27.
Alcohol-induced neuroinflammation is mediated by the innate immunesystem. Pro-inflammatory responses to alcohol are modulated by miRNAs. The miRNA miR-339-5p has previously been found to be upregulated in alcohol-induced neuroinflammation. However, little has been elucidated on the regulatory functions of this miRNA in alcohol-induced neuroinflammation. We investigated the function of miR-339-5p in alcohol exposed brain tissue and isolated microglial cells using ex vivo and in vitro techniques. Our results show that alcohol induces transcription of miR 339-5p, IL-6, IL-1β and TNF-α in mouse brain tissue and isolated microglial cells by activating NF-κB. Alcohol activation of NF-κB allows for nuclear translocation of the NF-κB subunit p65 and expression of pro-inflammatory mediators. miR-339-5p inhibited expression of these pro-inflammatory factors through the NF-κB pathway by abolishing IKK-β and IKK-ε activity.
酒精引起的神经炎症是由先天免疫系统介导的。miRNA 调节对酒精的促炎反应。miR-339-5p 先前被发现在上调酒精诱导的神经炎症中。然而,miR-339-5p 在酒精诱导的神经炎症中的调节功能还不太清楚。我们使用离体和体外技术研究了 miR-339-5p 在酒精暴露的脑组织和分离的小胶质细胞中的功能。我们的结果表明,酒精通过激活 NF-κB 诱导小鼠脑组织和分离的小胶质细胞中 miR 339-5p、IL-6、IL-1β 和 TNF-α 的转录。NF-κB 的激活允许 NF-κB 亚基 p65 和促炎介质的核易位。miR-339-5p 通过抑制 IKK-β 和 IKK-ε 的活性,通过 NF-κB 途径抑制这些促炎因子的表达。