Effects of hypnotic bromovalerylurea on microglial BV2 cells
Effects of hypnotic bromovalerylurea on microglial BV2 cells
复制标题
DOI：
10.1016/j.jphs.2017.05.007
复制
发表时间：
2017-06-01
影响因子：
3.5
通讯作者：
Tanaka, Junya
中科院分区：
文献类型：
--
作者：
Kawasaki, Shun;Abe, Naoki;Tanaka, Junya
溴戊酰脲（BU）是一种古老的镇静催眠药，具有抗炎作用。BU抑制一氧化氮（NO）的释放和促炎细胞因子的表达脂多糖（LPS）处理的BV 2细胞，小鼠小胶质细胞系。然而，BU不抑制LPS诱导的核因子-κ B核转位和随后的转录。BU抑制LPS诱导的信号转导和转录激活因子1（STAT 1）的磷酸化和干扰素调节因子1（IRF 1）的表达。Janus激酶1（JAK 1）抑制剂filgotinib抑制NO释放的作用比BU弱得多，尽管filgotinib几乎完全阻止了LPS诱导的STAT 1磷酸化。JAK 1，STAT 1，或IRF 1的敲除不影响BU对LPS诱导的BV 2细胞NO释放的抑制作用。BU和filgotinib的组合协同抑制NO释放。线粒体复合物I抑制剂鱼藤酮，这并没有阻止STAT 1磷酸化或IRF 1的表达，抑制促炎介质的表达比BU显着。BU和鱼藤酮降低细胞内ATP（iATP）水平的程度相似。鱼藤酮和filgotinib的组合抑制了LPS处理的BV 2细胞的NO释放，与BU一样强烈。这些结果表明，BU的抗炎作用可能归因于JAK 1/STAT 1依赖性通路的抑制和iATP水平的降低的协同作用。(C)2017作者制作和主办：Elsevier B. V.
An old sedative and hypnotic bromovalerylurea (BU) has anti-inflammatory effects. BU suppressed nitric oxide (NO) release and proinflammatory cytokine expression by lipopolysaccharide (LPS)-treated BV2 cells, a murine microglial cell line. However, BU did not inhibit LPS-induced nuclear translocation of nuclear factor-kappa B and subsequent transcription. BU suppressed LPS-induced phosphorylation of signal transducer and activator of transcription 1 (STAT1) and expression of interferon regulatory factor 1 (IRF1). The Janus kinase 1 (JAK1) inhibitor filgotinib suppressed the NO release much more weakly than that of BU, although filgotinib almost completely prevented LPS-induced STAT1 phosphorylation. Knockdown of JAK1, STAT1, or IRF1 did not affect the suppressive effects of BU on LPS-induced NO release by BV2 cells. A combination of BU and filgotinib synergistically suppressed the NO release. The mitochondrial complex I inhibitor rotenone, which did not prevent STAT1 phosphorylation or IRF1 expression, suppressed proinflammatory mediator expression less significantly than BU. BU and rotenone reduced intracellular ATP (iATP) levels to a similar extent. A combination of rotenone and filgotinib suppressed NO release by LPS-treated BV2 cells as strongly as BU. These results suggest that anti-inflammatory actions of BU may be attributable to the synergism of inhibition of JAK1/STAT1-dependent pathways and reduction in iATP level. (C) 2017 The Authors. Production and hosting by Elsevier B.V.