Histone deacetylase inhibitors suppress the expression of inflammatory and innate immune response genes in human microglia and astrocytes.

Histone deacetylase inhibitors suppress the expression of inflammatory and innate immune response genes in human microglia and astrocytes.
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DOI:
10.1007/s11481-010-9192-0
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发表时间:
2010-12
影响因子:
6.2
通讯作者:
Lee, Sunhee C.
Lee, Sunhee C.
中科院分区:
医学3区
文献类型:
--
作者:
Sub, Hyeon-Sook;Choi, Shinyeop;Khattar, Pallavi;Choi, Namjong;Lee, Sunhee C.

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组蛋白脱乙酰酶抑制物(HDACi)已被提出用于某些癌症的治疗和HIV+HAART患者的抗病毒治疗,但它们在胶质细胞炎症和先天抗病毒基因表达中的作用尚未确定。在这项研究中,我们研究了两种非选择性HDACi,曲古抑素A和丙戊酸,对TLR3或TLR4配体刺激的原代人小胶质细胞和星形胶质细胞抗病毒和细胞因子基因表达的影响。HDACi有效地抑制了天然抗病毒分子的表达,如干扰素β、干扰素模拟基因和参与TLR3/TLR4信号转导的蛋白质。HDACi还抑制小胶质细胞和星形细胞细胞因子和趋化因子基因的表达,但对不同组的细胞因子的影响不同。这些结果对HDACi的临床应用具有重要意义。
Histone deacetylase inhibitors (HDACi) have been proposed as therapies for certain cancers and as an anti-reservoir therapy for HIV+ individuals with HAART, yet, their roles in glial inflammatory and innate antiviral gene expression have not been defined. In this study, we examined the effects of two non-selective HDACi, trichostatin A and valproic acid, on antiviral and cytokine gene expression in primary human microglia and astrocytes stimulated with TLR3 or TLR4 ligand. HDACi potently suppressed the expression of innate antiviral molecules such as IFNβ, interferon-simulated genes, and proteins involved in TLR3/TLR4 signaling. HDACi also suppressed microglial and astrocytic cytokine and chemokine gene expression, but with different effects on different groups of cytokines. These results have important implications for the clinical use of HDACi.
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