Inhibition of HDAC6 alleviating lipopolysaccharide-induced p38MAPK phosphorylation and neuroinflammation in mice.
Inhibition of HDAC6 alleviating lipopolysaccharide-induced p38MAPK phosphorylation and neuroinflammation in mice.
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抑制 HDAC6 可减轻脂多糖诱导的 p38MAPK 磷酸化和小鼠神经炎症
DOI：
10.1080/13880209.2018.1563620
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发表时间：
2019-12
影响因子：
3.8
通讯作者：
Li L
中科院分区：
文献类型：
--
作者：
Song Y;Qin L;Yang R;Yang F;Kenechukwu NA;Zhao X;Zhou X;Wen X;Li L
抽象上下文：组蛋白去乙酰化酶6（HDAC 6）因其可加重炎症反应而受到各领域研究者的广泛关注。然而，有关HDAC 6是否会加剧脂多糖（LPS）诱导的炎症的研究仍然缺乏。目的：我们评估了HDAC 6在LPS诱导的脑炎症中的作用，并使用HDAC 6选择性抑制剂Tubastatin A（TBSA）进一步研究潜在的机制。材料与方法：昆明小鼠腹腔注射（I. P.），腹腔注射脂多糖（LPS）（1 mg/kg），经腹腔递送TBSA（0.5mg/kg）。免疫印迹法检测海马和皮质中磷酸化p38（p-p38）丝裂原活化蛋白激酶（MAPK）和典型炎症介质肿瘤坏死因子-α（TNF-α）和白细胞介素-6（IL-6）的表达。尼氏染色检测海马和皮层神经元损伤。结果：每天腹腔注射约1 mg/kg LPS（I. P.）注射12天显著增加p38 MAPK磷酸化、TNF-α和IL-6表达和神经元损失。然而，腹腔注射0.5 mg/kg TBSA（LPS处理前3天）15天可逆转上述结果。结论：TBSA能显著抑制LPS诱导的神经炎症反应和p-p38的表达。我们的研究结果可能有助于揭示通过抑制HDAC 6来抑制LPS诱导的脑炎症的有效靶向策略。
Abstract Context: Researchers in a variety of fields have extensively focused on histone deacetylase 6 (HDAC6) due to its aggravation of inflammatory reaction. However, relevant studies examining whether HDAC6 could exacerbate lipopolysaccharide (LPS)-induced inflammation are still lacking. Objective: We assessed the role of HDAC6 in LPS-induced brain inflammation and used the HDAC6-selective inhibitor Tubastatin A (TBSA) to investigate the potential mechanisms further. Materials and methods: Brain inflammation was induced in Kunming (KM) mice via intraperitoneal (I.P.), injection of Lipopolysaccharide (LPS) (1 mg/kg), the TBSA (0.5 mg/kg) was delivered via intraperitoneal. The phosphorylated p38 (p-p38) Mitogen-activated protein kinases (MAPK) and expression of typical inflammatory mediators, including tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in both the hippocampus and cortex, were examined by immunoblotting. Nissl staining was used to detect the neuronal damage in the hippocampus and the cortex. Results: About 1 mg/kg LPS via daily intraperitoneal (I.P.) injections for 12 days significantly increased p38 MAPK phosphorylation, TNF-α and IL-6 expression, and neuronal loss. However, 0.5 mg/kg TBSA (three days before LPS treatment) by I.P. injections for 15 days could reverse the above results. Conclusions: This present study provided evidence that TBSA significantly suppressed LPS-induced neuroinflammation and the expression of p-p38. Results derived from our study might help reveal the effective targeting strategies of LPS-induced brain inflammation through inhibiting HDAC6.
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影响因子：
2.7
作者：
Shen, Liangyun;Cui, Ziwei;Tan, Qian
通讯作者：
Tan, Qian
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影响因子：
5.1
作者：
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通讯作者：
Wang, Zhengtao
影响因子：
2.7
作者：
Fan Jianhua;Wei Wei;Wang Shao-Hui
通讯作者：
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3.7
作者：
Schwenkgrub J;Zaremba M;Joniec-Maciejak I;Cudna A;Mirowska-Guzel D;Kurkowska-Jastrzębska I
通讯作者：
Kurkowska-Jastrzębska I
影响因子：
2.9
作者：
Li, Dan;Liu, Nan;Li, Hong-Peng
通讯作者：
Li, Hong-Peng