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NFκB activation and stimulation of chemokine production in normal human macrophages by the gadolinium-based magnetic resonance contrast agent Omniscan: possible role in the pathogenesis of nephrogenic systemic fibrosis.
基于钆的磁共振对比剂 Omniscan 对正常人巨噬细胞中 nf κ b 的激活和趋化因子产生的刺激: 在肾源性系统性纤维化发病机制中的可能作用。

摘要

OBJECTIVE:Nephrogenic systemic fibrosis (NSF) is a generalised fibrotic disorder occurring in certain individuals with renal insufficiency exposed to gadolinium-based contrast agents (GdBCA) for MRI. Histopathological examination of affected tissues shows increased numbers of activated macrophages. To elucidate the mechanisms responsible for macrophage activation, the effects of the GdBCA Omniscan on normal human macrophage global gene expression, chemokine production and nuclear factor κB (NFκB) activation was examined.
METHODS:Normal human monocyte-derived macrophages were incubated with Omniscan (50 mM) and their gene expression analysed by microarrays and real-time PCR. Macrophage chemokine production was assayed by multiplex ELISA. NFκB activation was assessed by NFκB nuclear localisation and quantitation of intracellular levels of inducible nitric oxide synthase (iNOS) protein. A specific cell-permeable NFκB peptide inhibitor was used to abrogate NFκB stimulation of chemokine and iNOS protein levels. CCL8/MCP-2 in affected skin of patients with NSF was examined by indirect immunofluorescence.
RESULTS:Omniscan caused a profound change in the transcriptome of differentiated human normal macrophages in vitro, including a large increase in the expression of genes encoding CC and CXC chemokines. It induced rapid nuclear localisation of NFκB and stimulation of iNOS protein levels and chemokine production which were blocked by an NFκB inhibitory peptide. CCL8/MCP-2, the most upregulated chemokine following in vitro macrophage exposure to Omniscan, was strongly increased in NSF-affected skin.
CONCLUSION:The GdBCA Omniscan induces potent stimulation of macrophage gene expression, NFκB activation and increased NFκB-mediated production of CC and CXC chemokines and iNOS. These alterations may play a crucial role in the pathogenesis of NSF.

译文

目的: 肾源性系统性纤维化 (NSF) 是一种发生在某些肾功能不全的个体中,暴露于基于钆的 MRI 对比剂 (GdBCA)。受累组织的组织病理学检查显示活化巨噬细胞的数量增加。为了阐明巨噬细胞活化的机制,研究了 GdBCA Omniscan 对正常人巨噬细胞整体基因表达、趋化因子产生和核因子 κ b (nf κ b) 活化的影响。
方法: 正常人单核细胞来源的巨噬细胞与 Omniscan (50 毫米) 孵育,通过微阵列和 real-time PCR 分析其基因表达。用多重 ELISA 法检测巨噬细胞趋化因子的产生。通过 nf κ b 核定位和细胞内诱导型一氧化氮合酶 (iNOS) 蛋白水平的定量来评估 nf κ b 活化。使用一种特定的细胞渗透性 nf κ b 肽抑制剂来抑制 nf κ b 对趋化因子和 iNOS 蛋白水平的刺激。用间接免疫荧光检测 NSF 患者受累皮肤中的 CCL8/MCP-2。
结果: Omniscan 在体外引起了分化的人类正常巨噬细胞转录组的深刻变化,包括编码 CC 和 CXC 趋化因子的基因表达的大量增加。它诱导 nf κ b 的快速核定位和 iNOS 蛋白水平的刺激以及被 nf κ b 抑制肽阻断的趋化因子的产生。CCL8/MCP-2 是体外巨噬细胞暴露于 Omniscan 后最上调的趋化因子,在 NSF 影响的皮肤中强烈增加。
结论: GdBCA Omniscan 能有效刺激巨噬细胞基因表达、 nf κ b 活化,增加 nf κ b 介导的 CC 和 CXC 趋化因子和 iNOS 的产生。这些改变可能在 NSF 的发病机制中起关键作用。

Magnetic Resonance Contrast Agent

肾内泌尿 磁共振 临床研究术语
概述  :  

以医学成像为目的将某种特定物质引入人体内,以改变机体局部组织的影像对比度,这种被引入的物质称为“造影剂”(contrast medium,CM),目前称之为“对比剂”(contrast media)。磁共振对比剂(MR contrast agent)能特异或非特异性地改变组织的弛豫时间和信号强度,将有助于病变的早期诊断、小病灶的检出和对疾病的定性诊断。 临床分类 (1)根据细胞内、外分布分类:①细胞外对比剂:细胞外对比剂应用最早,日前应用也最

magnetic   英 [mægˈnetɪk]   美 [mægˈnetɪk]

释    义   adj. 地磁的;有磁性的;有吸引力的

例    句   But after getting the magnetic pulse, the volunteers tended to see nothing wrong with his actions - and judged his behaviour purely on whether his girlfriend survived.但在经受磁场刺激后,志愿者并不认为这种做法有任何不妥之处,而仅仅是根据他的女朋友是否幸存来评分。


resonance   英 [ˈrezənəns]   美 [ˈrezənəns]

释    义   n. [力]共振;共鸣;反响

例    句   Diagnosis was made via magnetic resonance imaging.是通过磁共振成像诊断的。


agent   英 [ˈeɪdʒənt]   美 [ˈeɪdʒənt]

释    义   n. 代理人,代理商;药剂;特工;动因

               vt. 由…作中介;由…代理

               adj. 代理的

例    句   This installs both the application and the agent.这会同时安装应用程序和代理。

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