Cytokine regulation of MMP-9 in peripheral glia: Implications for pathological processes and pain in injured nerve
Cytokine regulation of MMP-9 in peripheral glia: Implications for pathological processes and pain in injured nerve
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DOI：
10.1016/j.bbi.2006.10.015
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发表时间：
2007-07-01
影响因子：
15.1
通讯作者：
Shubayev, Veronica
中科院分区：
文献类型：
--
作者：
Chattopadhyay, Sharmila;Myers, Robert R.;Shubayev, Veronica
基质金属蛋白酶-9（MMP-9）是一种细胞外蛋白酶，其在周围神经损伤后数小时在雪旺细胞中被诱导，并控制轴突变性和巨噬细胞向病变的募集。在这里，我们报告了一个强大的（90倍）增加MMP-9 mRNA在大鼠坐骨神经挤压后24小时内（1至60天的时间过程）。使用直接注射到正常坐骨神经中，我们鉴定了促炎细胞因子TNF-α和IL-1 β作为MMP-9表达的有效调节剂（Taqman qPCR，酶谱法）。髓鞘形成的雪旺细胞产生MMP-9的细胞因子注射和挤压神经损伤的反应。MMP-9基因的缺失减少了未受刺激的神经性伤害性行为后一周的挤压和保护髓鞘的厚度，通过保护髓鞘碱性蛋白（MBP）的降解，通过蛋白质印迹和免疫荧光检测。这些数据表明，MMP-9在周围神经中的表达是由关键的促炎细胞因子途径控制的，并且其去除保护神经纤维免于脱髓鞘并减少损伤后的神经病理性疼痛。(c)2006年爱思唯尔公司All rights reserved.
Matrix metalloprotemase-9 (MMP-9) is an extracellular protease that is induced in Schwann cells hours after peripheral nerve injury and controls axonal degeneration and macrophage recruitment to the lesion. Here, we report a robust (90-fold) increase in MMP-9 mRNA within 24 h after rat sciatic nerve crush (1 to 60 days time-course). Using direct injection into a normal sciatic nerve, we identify the proinflammatory cytokines TNF-alpha and IL-1 beta as potent regulators of MMP-9 expression (Taqman qPCR, zymography). Myelinating Schwann cells produced MMP-9 in response to cytokine injection and crush nerve injury. MMP-9 gene deletion reduced unstimulated neuropathic nociceptive behavior after one week post-crush and preserved myelin thickness by protecting myelin basic protein (MBP) from degradation, tested by Western blot and immunofluorescence. These data suggest that MMP-9 expression in peripheral nerve is controlled by key proinflammatory cytokine pathways, and that its removal protects nerve fibers from demyelination and reduces neuropathic pain after injury. (c) 2006 Elsevier Inc. All rights reserved.