Histone deacetylase inhibitors suppress immune activation in primary mouse microglia
Histone deacetylase inhibitors suppress immune activation in primary mouse microglia
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DOI：
10.1002/jnr.23221
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发表时间：
2013-09-01
影响因子：
4.2
通讯作者：
Boddeke, Hendrikus W. G. M.
中科院分区：
文献类型：
--
作者：
Kannan, Vishnu;Brouwer, Nieske;Boddeke, Hendrikus W. G. M.
感染或损伤后的组织清除和修复需要神经炎症。为了防止过度损伤，关键是要限制神经炎症的程度，从而激活其主要效应细胞，小胶质细胞。CNS中两种主要的先天免疫细胞类型是星形胶质细胞和小胶质细胞。组蛋白去乙酰化酶（HDAC）参与调节先天性炎症反应，在这里，我们讨论了它们在纯星形胶质细胞和小胶质细胞培养中的作用。在小胶质细胞和星形胶质细胞中以及用脂多糖（LPS）或LPS和干扰素（IFN）处理后测定内源性HDAC表达水平。HDACs的相对表达水平在LPS或LPS/IFN（HDAC 1和-7除外）刺激的星形胶质细胞中降低，而在LPS处理后的小胶质细胞中增加，在原代培养物和从LPS处理的小鼠急性分离的小胶质细胞中，因此我们专注于小胶质细胞中的炎症反应。在存在或不存在HDAC抑制剂（HDACi）的情况下用LPS处理原代小胶质细胞培养物。通过定量RT-PCR、流式细胞术和ELISA测定炎性细胞因子的表达和释放。HDACi强烈抑制LPS诱导的细胞因子表达和小胶质细胞释放。此外，M1和M2相关的活化标记物的表达被抑制，并且小胶质细胞的迁移行为被减弱。我们的研究结果强烈表明HDACi抑制小胶质细胞中的先天免疫激活。(c)2013 Wiley Periodicals，Inc.
Neuroinflammation is required for tissue clearance and repair after infections or insults. To prevent excessive damage, it is crucial to limit the extent of neuroinflammation and thereby the activation of its principal effector cell, microglia. The two main major innate immune cell types in the CNS are astrocytes and microglia. Histone deacetylases (HDACs) have been implicated in regulating the innate inflammatory response, and here we addressed their role in pure astrocyte and microglia cultures. Endogenous HDAC expression levels were determined in microglia and astrocytes and after treatment with lipopolysaccharide (LPS) or LPS and interferon (IFN). The relative expression level of HDACs was reduced in LPS- or LPS/IFN (with the exception of HDAC1 and -7)-stimulated astrocytes and increased in microglia after LPS treatment both in primary cultures and in microglia acutely isolated from LPS-treated mice, so we focused on the inflammatory response in microglia. Primary microglia cultures were treated with LPS in the presence or absence of HDAC inhibitors (HDACi). Expression and release of inflammatory cytokines was determined by quantitative RT-PCR, flow cytometry, and ELISA. HDACi strongly suppressed LPS-induced cytokine expression and release by microglia. Furthermore, expression of M1- and M2-associated activation markers was suppressed, and the migratory behavior of microglia was attenuated. Our findings strongly suggest that HDACi suppress innate immune activation in microglia. (c) 2013 Wiley Periodicals, Inc.