Isomeranzin suppresses inflammation by inhibiting M1 macrophage polarization through the NF-κB and ERK pathway
Isomeranzin suppresses inflammation by inhibiting M1 macrophage polarization through the NF-κB and ERK pathway
复制标题
Isomeranzin 通过 NF-kappaB 和 ERK 通路抑制 M1 巨噬细胞极化，从而抑制炎症。
DOI：
10.1016/j.intimp.2016.05.027
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发表时间：
2016-09-01
影响因子：
5.6
通讯作者：
Xu, Qiang
中科院分区：
文献类型：
--
作者：
Xu, Ge;Feng, Lili;Xu, Qiang
巨噬细胞极化在炎症中起重要作用。据报道，极化的调节是各种炎性疾病的有效治疗剂。本研究的目的是探讨九里香异黄酮苷的抗炎活性及其可能的分子机制。结果表明，异丙甲素通过下调NF-κ B和ERK信号特异性地降低M1巨噬细胞相关的促炎细胞因子。免疫沉淀和RNA沉默实验表明，异丙肼抑制NF-κ B B活化依赖于TRAF 6泛素化的减少。体内研究表明，异丙嗪能明显抑制LPS诱导的脓毒症，提高存活率，改善组织损伤，减少炎性细胞因子。根据体外研究，isomeranzin显著阻断肺和肝组织中p-p65和p-ERK的表达。此外，isomeranzin改善DSS和TNBS诱导的结肠炎，由于其抗炎作用。综上所述，异构肼通过NF-κ B和ERK途径控制M1巨噬细胞极化来抑制炎性疾病。(C)© 2016 Elsevier B.V.版权所有。
Macrophage polarization plays an important role in inflammation. Regulation of the polarization has been reported to be effective therapeutics for various kinds of inflammatory diseases. The aims of the present study were to investigate the anti-inflammatory property of isomeranzin isolating from Murraya exotica as well as potential molecular mechanisms. Results showed that isomeranzin specifically reduced the M1 macrophage-associated pro-inflammatory cytokines through down-regulation of NF-kappa B and ERK signals. Immunoprecipitation and RNA silencing indicated suppression of isomeranzin in NF-kappa B activation was relying on the decreasing of TRAF6 ubiquitination. In vivo studies showed isomeranzin evidently inhibited LPS-induced sepsis for rising survival rate, improving tissue damage and lessening inflammatory cytokines. In accordance with in vitro studies, isomeranzin significantly blocked expression of p-p65 and p-ERK in lung and liver tissues. Moreover, isomeranzin ameliorated DSS and TNBS-induced colitis due to its anti-inflammatory effects. Taken together, isomeranzin suppressed inflammatory diseases by controlling M1 macrophage polarization through the NF-kappa B and ERK pathway. (C) 2016 Elsevier B.V. All rights reserved.