Interleukin-1β pre-treated bone marrow stromal cells alleviate neuropathic pain through CCL7-mediated inhibition of microglial activation in the spinal cord.
Interleukin-1β pre-treated bone marrow stromal cells alleviate neuropathic pain through CCL7-mediated inhibition of microglial activation in the spinal cord.
复制标题
Interleukin-1 beta 预处理的骨髓基质细胞通过 CCL7 介导的脊髓小胶质细胞激活抑制减轻神经性疼痛
DOI：
10.1038/srep42260
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发表时间：
2017-02-14
影响因子：
4.6
通讯作者：
Yuan H
中科院分区：
文献类型：
--
作者：
Li J;Deng G;Wang H;Yang M;Yang R;Li X;Zhang X;Yuan H
虽然神经性疼痛是最难治疗的疾病之一，但最近的研究表明，全身或局部注射骨髓基质细胞（BMSCs）减少促炎细胞因子的释放，减轻神经性疼痛。然而，目前尚不清楚预处理的BMSC是否具有强烈的抗炎和/或镇痛作用。采用脊神经结扎致神经病理性疼痛模型，将IL-1β预处理的BMSCs（IL-1β-BMSCs）注射到大鼠体内，观察SNL对神经病理性疼痛的影响。结果表明，IL-1β-BMSCs在改善神经病理性疼痛和抑制小胶质细胞活化方面均更有效。具体地，发现小胶质细胞抑制由趋化因子C-C基序配体7（CCL 7）而不是CCL 2介导。IL-1β-BMSCs对星形胶质细胞的活化和CCL 7的释放有较强的抑制作用，其抑制作用由IL-10介导，而不是由转化生长因子-β1介导。此外，我们还发现SNL后C-X-C基序趋化因子配体（CXCL）13表达增加，介导IL-1β-BMSCs定向迁移。结论：IL-1β-BMSCs可通过降低脊髓组织中CCL 7的表达，抑制小胶质细胞的活化，从而抑制神经病理性疼痛。
Although neuropathic pain is one of the most intractable diseases, recent studies indicate that systemic or local injection of bone marrow stromal cells (BMSCs) decreases pro-inflammatory cytokines release and alleviates neuropathic pain. However, it is still not clear whether pre-treated BMSCs have a strong anti-inflammatory and/or analgesia effect. Using the spinal nerve ligation model of neuropathic pain, IL-1β pre-treated BMSCs (IL-1β-BMSCs) were injected into rats followed by SNL in order to determine possible effects. Results indicated that IL-1β-BMSCs were more efficacious in both amelioration of neuropathic pain and inhibition of microglia activation. Specifically, microglia inhibition was found to be mediated by chemokine C-C motif ligand 7 (CCL7) but not CCL2. Results also showed that IL-1β-BMSCs had a stronger inhibitory effect on astrocyte activation as well as CCL7 release, which was found to be mediated by IL-10 not transforming growth factor-β1. In addition, we also found directional migration of IL-1β-BMSCs was mediated by inceased C-X-C motif chemokine ligand (CXCL) 13 expression following SNL. In conclusion, our results indicated IL-1β-BMSCs could inhibit microglia activation and neuropathic pain by decreasing CCL7 level in spinal cord.