Interleukin-1β pre-treated bone marrow stromal cells alleviate neuropathic pain through CCL7-mediated inhibition of microglial activation in the spinal cord

白细胞介素-1β预处理的骨髓基质细胞通过CCL7介导的抑制脊髓小胶质细胞活化来缓解神经性疼痛

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作者:Jian Li, Guoying Deng, Haowei Wang, Mei Yang, Rui Yang, Xiangnan Li, Xiaoping Zhang, Hongbin Yuan

Abstract

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.

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