Budlein A from Viguiera robusta inhibits leukocyte-endothelial cell interactions, adhesion molecule expression and inflammatory mediators release
Budlein A from Viguiera robusta inhibits leukocyte-endothelial cell interactions, adhesion molecule expression and inflammatory mediators release
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DOI：
10.1016/j.phymed.2009.04.002
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发表时间：
2009-10-01
期刊：
影响因子：
7.9
通讯作者：
Faccioli, Lucia H.
中科院分区：
文献类型：
--
作者：
Nicolete, Roberto;Arakawa, Nilton S.;Faccioli, Lucia H.
据报道，Budlein A具有一定的镇痛和抗炎特性。在这项研究中，我们已经评估了其对LPS诱导的白细胞募集的影响，并参与其抗炎活性的机制。在体内，活体视频显微镜被用来确定芽素A对LPS诱导的小鼠提睾肌微循环中的白细胞-内皮细胞相互作用的影响。在体外，Budlein A对LPS诱导的细胞因子，趋化因子和亚硝酸盐释放，T细胞增殖反应以及细胞粘附分子（CAM）表达的影响进行了评估。在体内，腹腔内注射的Budlein A（2.6 mM/kg）引起了显着减少LPS诱导的白细胞滚动流量，粘附和迁出分别为84%，92%和96%。在体外，T细胞增殖反应也受到Budlein A的影响。当小鼠J774巨噬细胞与倍半萜内酯一起孵育时，LPS诱导的IL-1 β、肿瘤坏死因子-α（TNF-α）和角质形成细胞衍生的趋化因子（KC）释放受到浓度依赖性抑制。在人脐静脉内皮细胞（HUVECs）中，芽肽A还减少TNF-α、单核细胞趋化蛋白-1（MCP-1）、IL-8、亚硝酸盐和由LPS引起的CAM表达的产生。Budlein A是体内LPS诱导的白细胞积聚的有效抑制剂。这种作用似乎是通过抑制细胞因子和趋化因子释放以及下调CAM表达来介导的。因此，它具有潜在的治疗兴趣，控制白细胞募集发生在不同的炎症性疾病。(C)2009年Elsevier GrnbH。All rights reserved.
Budlein A has been reported to exert some analgesic and anti-inflammatory properties. In this study, we have evaluated its effect on LPS-induced leukocyte recruitment in vivo and the mechanisms involved in its anti-inflammatory activity. In vivo, intravital videomicroscopy was used to determine the effects of budlein A on LPS-induced leukocyte-endothelial cell interactions in the murine cremasteric microcirculation. In vitro, the effects of budlein A on LPS-induced cytokine, chemokine and nitrites release, T-cell proliferative response as well as cell adhesion molecule expression (CAM) were evaluated. In vivo, intraperitoneal administration of budlein A (2.6 mM/kg) caused a significant reduction of LPS-induced leukocyte rolling flux, adhesion and emigration by 84, 92 and 96% respectively. In vitro, T-cell proliferative response was also affected by budlein A. When murine J774 macrophages were incubated with the sesquiterpene lactone, LPS-induced IL-1 beta, tumor necrosis factor-alpha (TNF-alpha) and keratinocyte-derived chemokine (KC) release were concentration-dependently inhibited. In human umbilical vein endothelial cells (HUVECs), budlein A also reduced the production of TNF-alpha, monocyte chemoattractant protein-1 (MCP-1), IL-8, nitrites and CAM expression elicited by LPS. Budlein A is a potent inhibitor of LPS-induced leukocyte accumulation in vivo. This effect appears to be mediated through inhibition of cytokine and chemokine release and down-regulation of CAM expression. Thus, it has potential therapeutic interest for the control of leukocyte recruitment that occurs in different inflammatory disorders. (C) 2009 Elsevier GrnbH. All rights reserved.