Toll-like receptor 2 contributes to chemokine gene expression and macrophage infiltration in the dorsal root ganglia after peripheral nerve injury.

Toll-like receptor 2 contributes to chemokine gene expression and macrophage infiltration in the dorsal root ganglia after peripheral nerve injury.
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DOI:
10.1186/1744-8069-7-74
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发表时间:
2011-09-28
期刊:
影响因子:
3.3
通讯作者:
Lee SJ
Lee SJ
中科院分区:
医学3区
文献类型:
--
作者:
Kim D;You B;Lim H;Lee SJ

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我们之前已经报道,在Toll样受体2(TLR2)基因敲除的小鼠中,神经损伤引起的神经病理性疼痛得到缓解。在这些小鼠中,炎症基因的表达和脊髓小胶质细胞的激活受到了影响,而在背根神经节(DRG)中的影响尚未得到测试。在本研究中,我们研究了TLR2在周围神经损伤后背根神经节炎症反应中的作用。L5脊神经横断损伤可诱导CCL2/MCP-1和CCL3/MIP-1等巨噬细胞趋化因子在野生型小鼠背根神经节表达,随后巨噬细胞在背根节内大量浸润。然而,在TLR2基因敲除的小鼠中,神经损伤后趋化因子的诱导表达和巨噬细胞的浸润明显减少。同样,在TLR2基因敲除小鼠中,脊神经损伤诱导的脊神经节中IL-1β和肿瘤坏死因子-α的表达也得到了改善。在TLR2基因敲除小鼠中,背根神经节炎症反应的减少伴随着神经损伤诱导的自发疼痛超敏反应的减弱。我们的研究结果表明,TLR2参与了神经损伤诱导的促炎性趋化因子/细胞因子基因表达和巨噬细胞在背根节的浸润,这可能与TLR2基因敲除小鼠脊髓神经损伤后疼痛超敏反应的降低有关。
We have previously reported that nerve injury-induced neuropathic pain is attenuated in toll-like receptor 2 (TLR2) knock-out mice. In these mice, inflammatory gene expression and spinal cord microglia actvation is compromised, whereas the effects in the dorsal root ganglia (DRG) have not been tested. In this study, we investigated the role of TLR2 in inflammatory responses in the DRG after peripheral nerve injury. L5 spinal nerve transection injury induced the expression of macrophage-attracting chemokines such as CCL2/MCP-1 and CCL3/MIP-1 and subsequent macrophage infiltration in the DRG of wild-type mice. In TLR2 knock-out mice, however, the induction of chemokine expression and macrophage infiltration following nerve injury were markedly reduced. Similarly, the induction of IL-1β and TNF-α expression in the DRG by spinal nerve injury was ameliorated in TLR2 knock-out mice. The reduced inflammatory response in the DRG was accompanied by attenuation of nerve injury-induced spontaneous pain hypersensitivity in TLR2 knock-out mice. Our data show that TLR2 contributes to nerve injury-induced proinflammatory chemokine/cytokine gene expression and macrophage infiltration in the DRG, which may have relevance in the reduced pain hypersensitivity in TLR2 knock-out mice after spinal nerve injury.
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