首页> 美国卫生研究院文献>Toxicological Research >Gambogic Acid Disrupts Toll-like Receptor4 Activation by Blocking Lipopolysaccharides Binding to Myeloid Differentiation Factor 2
【2h】

Gambogic Acid Disrupts Toll-like Receptor4 Activation by Blocking Lipopolysaccharides Binding to Myeloid Differentiation Factor 2

机译:藤黄酸通过阻断脂多糖与髓样分化因子2结合来破坏Toll样受体4的激活。

代理获取
本网站仅为用户提供外文OA文献查询和代理获取服务,本网站没有原文。下单后我们将采用程序或人工为您竭诚获取高质量的原文,但由于OA文献来源多样且变更频繁,仍可能出现获取不到、文献不完整或与标题不符等情况,如果获取不到我们将提供退款服务。请知悉。

摘要

Our body’s immune system has defense mechanisms against pathogens such as viruses and bacteria. Immune responses are primarily initiated by the activation of toll-like receptors (TLRs). In particular, TLR4 is well-characterized and is known to be activated by gram-negative bacteria and tissue damage signals. TLR4 requires myeloid differentiation factor 2 (MD2) as a co-receptor to recognize its ligand, lipopolysaccharides (LPS), which is an extracellular membrane component of gram-negative bacteria. Gambogic acid is a xanthonoid isolated from brownish or orange resin extracted from Garcinia hanburyi. Its primary effect is tumor suppression. Since inflammatory responses are related to the development of cancer, we hypothesized that gambogic acid may regulate TLR4 activation. Our results demonstrated that gambogic acid decreased the expression of pro-inflammatory cytokines (TNF-α, IL-6, IL-12, and IL-1β) in both mRNA and protein levels in bone marrow-derived primary macrophages after stimulation with LPS. Gambogic acid did not inhibit the activation of Interferon regulatory factor 3 (IRF3) induced by TBK1 overexpression in a luciferase reporter gene assay using IFN-β-PRD III-I-luc. An in vitro kinase assay using recombinant TBK1 revealed that gambogic acid did not directly inhibit TBK1 kinase activity, and instead suppressed the binding of LPS to MD2, as determined by an in vitro binding assay and confocal microscopy analysis. Together, our results demonstrate that gambogic acid disrupts LPS interaction with the TLR4/MD2 complex, the novel mechanism by which it suppresses TLR4 activation.
机译:人体的免疫系统具有防御机制,可抵抗病毒和细菌等病原体。免疫反应主要是由Toll样受体(TLR)的激活引发的。特别是,TLR4具有充分的特征,并且已知会被革兰氏阴性细菌和组织损伤信号激活。 TLR4需要髓样分化因子2(MD2)作为共受体才能识别其配体脂多糖(LPS),脂多糖是革兰氏阴性细菌的细胞外膜成分。藤黄酸是一种类黄酮类化合物,是从汉黄藤黄提取的褐色或橙色树脂中分离出来的。它的主要作用是抑制肿瘤。由于炎症反应与癌症的发展有关,我们假设藤黄酸可能调节TLR4的活化。我们的结果表明,藤黄酸在LPS刺激后可降低骨髓来源的原代巨噬细胞mRNA和蛋白水平中促炎性细胞因子(TNF-α,IL-6,IL-12和IL-1β)的表达。在使用IFN-β-PRDIII-I-luc的荧光素酶报告基因试验中,藤黄酸不抑制由TBK1过表达诱导的干扰素调节因子3(IRF3)的激活。使用重组TBK1进行的体外激酶测定显示,藤黄酸不直接抑制TBK1激酶活性,而是通过体外结合测定和共聚焦显微镜分析确定了抑制LPS与MD2的结合。在一起,我们的结果表明,藤黄酸破坏了与TLR4 / MD2复合物的LPS相互作用,这是它抑制TLR4活化的新机制。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
代理获取

客服邮箱:kefu@zhangqiaokeyan.com

京公网安备:11010802029741号 ICP备案号:京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有
  • 客服微信

  • 服务号