首页> 外文期刊>Journal of Neuroimmunology: Official Bulletin of the Research Committee on Neuroimmunology of the World Federation of Neurology >N-adamantyl-4-methylthiazol-2-amine suppresses lipopolysaccharide-induced brain inflammation by regulating NF-kappa B signaling in mice
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N-adamantyl-4-methylthiazol-2-amine suppresses lipopolysaccharide-induced brain inflammation by regulating NF-kappa B signaling in mice

机译:N-金刚烷基-4-甲基噻唑-2-胺通过调节小鼠的NF-κB信号传导抑制脂多糖诱导的脑部炎症

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We report that N-adamanty1-4-methylthiazol-2-amine (KHG26693), a novel thiazole derivative, can prevent lipopolysaccharide (LPS)-induced brain inflammation in mice. In this LPS-induced model of brain inflammation, administration of KHG26693 effectively prevented increases in the levels of IL-1 beta, TNF-alpha, prostaglandin E2, malondialdehyde, and nitric oxide, and mitigated reductions in the levels of superoxide dismutase in the hippocampus. KHG26693 also prevented reductions in the levels of hippocampal brain-derived neurotrophic factors. Furthermore, pretreatment with KHG26693 prior to LPS treatment dramatically attenuated the elevation of inducible nitric oxide synthase and cyclooxygenase-2 protein levels. Moreover, pretreatment with KHG26693 significantly suppressed LPS-induced phosphorylation of NF-kappa B and I kappa B alpha through the inactivation of IKK beta. Additionally, KHG26693 caused the downregulation of LPS-induced cystathionine-b-synthase gene expression in the brain. Although the clinical relevance of our findings remains to be determined, our data suggest that KHG26693 might prevent neuronal cell injury via the reduction of inflammation and oxidative stress in the brain. (C) 2015 Elsevier B.V. All rights reserved.
机译:我们报告N-adamanty1-4-甲基噻唑-2-胺(KHG26693),一种新型的噻唑衍生物,可以预防脂多糖(LPS)诱导的小鼠脑部炎症。在这种LPS诱导的脑炎症模型中,施用KHG26693可有效防止IL-1β,TNF-α,前列腺素E2,丙二醛和一氧化氮水平的升高,并减轻海马中超氧化物歧化酶水平的降低。 KHG26693还防止海马脑源性神经营养因子水平的降低。此外,在LPS处理之前用KHG26693进行预处理可显着降低诱导型一氧化氮合酶和环氧合酶2蛋白的水平。此外,用KHG26693预处理可通过IKK beta的失活显着抑制LPS诱导的NF-κB和IκBα的磷酸化。此外,KHG26693导致LPS诱导的脑中胱硫醚b-合酶基因表达下调。尽管我们发现的临床相关性尚待确定,但我们的数据表明KHG26693可能通过减少大脑中的炎症和氧化应激来预防神经元细胞损伤。 (C)2015 Elsevier B.V.保留所有权利。

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