Andrographolide inhibits HMGB1-induced inflammatory responses in human umbilical vein endothelial cells and in murine polymicrobial sepsis
Andrographolide inhibits HMGB1-induced inflammatory responses in human umbilical vein endothelial cells and in murine polymicrobial sepsis
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DOI：
10.1111/apha.12264
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发表时间：
2014-05-01
影响因子：
6.3
通讯作者：
Bae, J.
中科院分区：
文献类型：
--
作者：
Lee, W.;Ku, S.;Bae, J.
核DNA结合蛋白高迁移率族蛋白1（HMGB 1）蛋白作为严重血管炎性疾病（如感染性休克）的晚期介质，上调促炎细胞因子。穿心莲是从穿心莲属植物中分离出来的一种民间药物，用于治疗病毒感染、腹泻、痢疾和发热。然而，AG对HMGB 1诱导的炎症反应的影响尚未研究。我们通过监测治疗后AG对脂多糖（LPS）和盲肠结扎穿孔（CLP）介导的HMGB 1释放以及HMGB 1介导的人脐静脉内皮细胞（HUVECs）和脓毒症小鼠促炎反应调节的影响来评估这个问题。HMGB 1介导的释放和HMGB 1介导的细胞骨架重排。AG还抑制HMGB 1介导的高通透性和白细胞迁移在败血症小鼠。此外，AG抑制HUVECs中肿瘤坏死因子（TNF-α）的产生以及HMGB 1对AKT、核因子-B（NF-B）和细胞外调节激酶（ERK）1/2的激活。AG还诱导下调CLP诱导的HMGB 1的释放，白细胞介素（IL）1/6/8和mortality.ConclusionCollectively的生产，这些结果表明，AG可以被视为一个候选的治疗药物通过抑制HMGB 1信号通路的血管炎性疾病的治疗。
AimNuclear DNA-binding protein high-mobility group box 1 (HMGB1) protein acts as a late mediator of severe vascular inflammatory conditions, such as septic shock, upregulating pro-inflammatory cytokines. Andrographolide (AG) is isolated from the plant of Andrographis paniculata and used as a folk medicine for treatment of viral infection, diarrhoea, dysentery and fever. However, the effect of AG on HMGB1-induced inflammatory response has not been studied.MethodsFirstly, we accessed this question by monitoring the effects of post-treatment AG on lipopolysaccharide (LPS) and caecal ligation and puncture (CLP)-mediated release of HMGB1 and HMGB1-mediated regulation of pro-inflammatory responses in human umbilical vein endothelial cells (HUVECs) and septic mice.ResultsPost-treatment AG was found to suppress LPS-mediated release of HMGB1 and HMGB1-mediated cytoskeletal rearrangements. AG also inhibited HMGB1-mediated hyperpermeability and leucocyte migration in septic mice. In addition, AG inhibited production of tumour necrosis factor- (TNF-) and activation of AKT, nuclear factor-B (NF-B) and extracellular-regulated kinases (ERK) 1/2 by HMGB1 in HUVECs. AG also induced downregulation of CLP-induced release of HMGB1, production of interleukin (IL) 1/6/8 and mortality.ConclusionCollectively, these results suggest that AG may be regarded as a candidate therapeutic agent for the treatment of vascular inflammatory diseases via inhibition of the HMGB1 signalling pathway.