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首页> 外文期刊>International immunopharmacology >Suppressive effects of 1-[4-fluoro-2-(2-nitrovinyl)phenyl]pyrrolidine on the Toll-like receptor signaling pathways
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Suppressive effects of 1-[4-fluoro-2-(2-nitrovinyl)phenyl]pyrrolidine on the Toll-like receptor signaling pathways

机译:1- [4-氟-2-(2-硝基乙烯基)苯基]吡咯烷对Toll样受体信号转导通路的抑制作用

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摘要

When various pathogens invade a host, toll-like receptors (TLRs) play a significant role in recognizing the pathogen-associated molecular patterns carried by the pathogens to induce innate immune reaction, followed by acquired immunity reaction. TLRs have two downstream signaling pathways, the myeloid differential factor 88 (MyD88)-dependent and toll-interleukin-1 receptor domain-containing adapter inducing interferon-beta (TRIF)-dependent pathways. To evaluate the therapeutic potential of 1-[4-fluoro-2-(2-nitrovinyl)phenyl]pyrrolidine (FPP), previously synthesized in our laboratory, its effect on signal transduction via the TLR signaling pathways was examined. FPP inhibited the activation of nuclear factor-kappa B (NF-kappa B) and interferon regulatory factor 3 (IRF3) induced by TLR agonists, as well as inhibited the expression of cydooxygenase-2, inducible nitric oxide synthase, and interferon inducible protein-10. FPP also inhibited the activation of NF-kappa B and IRF3 when induced by the overexpression of downstream signaling components of the TLRs. As a result, FPP has potential to become a new therapeutic drug for many inflammatory diseases. (C) 2014 Elsevier B.V. All rights reserved.
机译:当各种病原体入侵宿主时,toll​​样受体(TLR)在识别病原体携带的与病原体相关的分子模式以诱导先天性免疫反应,继之以获得性免疫反应中起重要作用。 TLR具有两个下游信号传导途径,即髓样分化因子88(MyD88)依赖性和含toll-IL-1受体域的衔接子诱导干扰素-β(TRIF)依赖性途径。为了评估以前在我们实验室中合成的1- [4-氟-2-(2-硝基乙烯基)苯基]吡咯烷(FPP)的治疗潜力,研究了其对通过TLR信号通路进行的信号传导的影响。 FPP抑制TLR激动剂诱导的核因子-κB(NF-κB)和干扰素调节因子3(IRF3)的激活,并抑制cydooxygenase-2,诱导型一氧化氮合酶和干扰素诱导的蛋白10。当由TLR下游信号成分的过表达诱导时,FPP还抑制NF-κB和IRF3的激活。因此,FPP有潜力成为许多炎症性疾病的新治疗药物。 (C)2014 Elsevier B.V.保留所有权利。

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