Expression of myeloid differentiation primary response protein 88 (Myd88) in the cerebral cortex after experimental traumatic brain injury in rats
Expression of myeloid differentiation primary response protein 88 (Myd88) in the cerebral cortex after experimental traumatic brain injury in rats
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DOI：
10.1016/j.brainres.2011.04.014
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发表时间：
2011-06-17
期刊：
影响因子：
2.9
通讯作者：
Hang, Chun-Hua
中科院分区：
文献类型：
--
作者：
Li, Guang-Zhao;Zhang, Yang;Hang, Chun-Hua
越来越多的证据表明，Toll样受体（TLR）和白细胞介素-1（IL-1）家族参与了与中风、感染、肿瘤和其他中枢神经系统疾病相关的损伤性炎症过程。髓样分化初级应答蛋白88（Myd 88）是一种重要的接头蛋白，它传递TLR和IL-1家族的信号。因此，本研究旨在检测Myd 88蛋白和mRNA在大鼠失重性脑损伤模型中的表达，探讨Myd 88在创伤性脑损伤（TBI）中的作用。将54只Sprague道利（SD）大鼠随机分为对照组和TBI组。TBI组采用改良Feeney模型进行实验性TBI。通过逆转录PCR（RT-PCR）、蛋白质印迹分析和免疫组织化学测量Myd 88表达;（NF-κ B）结合活性，通过电泳迁移率变动分析（EMSA）;肿瘤坏死因子-α水平（TNF-α）和白细胞介素1 β采用酶联免疫吸附法（ELISA）检测IL-1 β的表达，免疫组化法检测细胞间粘附分子-1（ICAM-1）的表达。Myd 88在脑损伤后6 h和7 d表达明显增加，3 d达高峰。NF-κ B、TNF-α、IL-1 β。ICAM-1在脑损伤后也明显升高。我们的数据表明，Myd 88的表达增加与NF-κ B B，促炎细胞因子和ICAM-1的上调平行，并且它们之间存在高度正相关。这些发现可能在特定Myd 88拮抗剂给药期间具有重要意义，以预防或减少TBI后的炎症反应。(C)2011 Elsevier B. V.保留所有权利。
A growing body of evidence indicates that Toll-like receptors (TLRs) and Interleukin-1 (IL-1) family have been shown to be involved in the damaging inflammatory processes associated with stroke, infection, neoplasia, and other diseases in the central nervous system. Myeloid differentiation primary response protein 88 (Myd88) is a critical adaptor protein that transmits signals for TLRs and IL-1 family. Therefore, this study aimed to detect the expression of Myd88 protein and mRNA in a rat weight-dropping trauma model and to clarify the role of Myd88 after traumatic brain injury (TBI). A total of fifty-four Sprague Dawley (SD) rats were randomly divided into control group and TBI groups at hours 6, 12 and on day 1, day 2, day 3, and day 7. The TBI groups suffered experimental TBI by improved Feeney model. Myd88 expression is measured by Reverse Transcription PCR (RT-PCR), Western blot analysis and immunohistochemistry; and nuclear factor-kappaB (NF-kappa B) binding activity by electrophoretic mobility shift assay (EMSA); The levels of tumor necrosis factor-alpha (TNF-alpha) and Interleukin 1 beta (IL-1 beta) were measured by enzyme linked immunosorbent assay (ELISA) and the intercellular adhesion molecule-1 (ICAM-1) expression by immunohistochemistry. The expression of Myd88 in the injured brain was dramatically increased through 6 h and 7 days postinjury, and peaked on 3 days. NF-kappa B, TNF-alpha, IL-1 beta. and ICAM-1 also ascended significantly after TBI. Our data demonstrated that Myd88 was increasingly expressed in a parallel time course to the up-regulation of NF-kappa B, proinflammatory cytokines and ICAM-1 and there was a highly positive relationship among them. These findings might have important implications during the administration of specific Myd88 antagonists in order to prevent or reduce inflammatory response after TBI. (C) 2011 Elsevier B.V. All rights reserved.