Effects of a pyrrole-based, microtubule-depolymerizing compound on RAW 264.7 macrophages.
Effects of a pyrrole-based, microtubule-depolymerizing compound on RAW 264.7 macrophages.
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DOI：
10.1016/j.cbi.2016.01.009
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发表时间：
2016-02-25
影响因子：
5.1
通讯作者：
Fischer-Stenger K
中科院分区：
文献类型：
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作者：
Ciemniecki JA;Lewis CP;Gupton JT;Fischer-Stenger K
将 RAW 264.7 小鼠巨噬细胞暴露于基于吡咯的化合物 3,5-二溴-4-(3,4-二甲氧基苯基)-1H-吡咯-2-羧酸乙酯 (JG-03-14)，这是一种已知的具有抗肿瘤活性的微管解聚剂。在这项研究中，暴露于 JG-03-14 会减少脂多糖 (LPS) 激活的巨噬细胞产生促炎分子。使用基于吡咯的化合物进行治疗可降低巨噬细胞释放的肿瘤坏死因子-α (TNF-α) 和一氧化氮 (NO) 的浓度。暴露于 JG-03-14 还降低了 TNF-α mRNA 表达水平和诱导型一氧化氮合酶 (iNOS) 的蛋白质表达水平，iNOS 是活化巨噬细胞中负责生成 NO 的酶。此外，JG-03-14 治疗显着改变了 IκB-β（NF-κB 转录因子抑制剂）的降解情况，这表明 JG-03-14 可能会减弱 LPS 诱导的 NF-κB 信号通路的激活，该信号通路是产生促炎介质所需的。我们得出结论，JG-03-14 具有抗炎特性。
RAW 264.7 murine macrophages were exposed to the pyrrole-based compound 3,5-Dibromo-4-(3,4-dimethoxyphenyl)-1H-pyrrole-2-carboxylic acid ethyl ester (JG-03-14), which is a known microtubule depolymerizing agent with antitumor activity. In this study exposure to JG-03-14 reduced the production of pro-inflammatory molecules by macrophages activated with lipopolysaccharide (LPS). Treatment with the pyrrole-based compound decreased the concentration of tumor necrosis factor-α (TNF-α) and nitric oxide (NO) released from the macrophages. Exposure to JG-03-14 also decreased TNF-α mRNA expression levels and the protein expression levels of inducible nitric oxide synthase (iNOS), the enzyme responsible for NO production in the activated macrophages. Furthermore, JG-03-14 treatment significantly changed the degradation profile of IκB-β, an inhibitor of the NF-κB transcription factor, which suggests that JG-03-14 may attenuate the activation of the LPS-induced NF-κB signaling pathway needed to produce the pro-inflammatory mediators. We conclude that JG-03-14 possesses anti-inflammatory properties.