Department of Pathology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
J Neuroimmune Pharmacol. 2010 Dec;5(4):521-32. doi: 10.1007/s11481-010-9192-0. Epub 2010 Feb 17.
Histone deacetylase inhibitors (HDACi) have been proposed as therapies for certain cancers and as an anti-reservoir therapy for HIV+ individuals with highly active anti-retroviral therapy, 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.
组蛋白去乙酰化酶抑制剂（HDACi）已被提议用于治疗某些癌症，并作为高效抗逆转录病毒疗法的 HIV+个体的抗储库治疗，但它们在神经胶质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，曲古抑菌素 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中抗病毒和细胞因子基因表达的影响。HDACi 强烈抑制了先天抗病毒分子的表达，如 IFNβ、干扰素刺激基因以及参与 TLR3/TLR4 信号转导的蛋白。HDACi 还抑制了小胶质细胞和星形胶质细胞细胞因子和趋化因子基因的表达，但对不同细胞因子组的影响不同。这些结果对 HDACi 的临床应用具有重要意义。
