Tumor necrosis factor receptor 1 induces interleukin-6 upregulation through NF-kappaB in a rat neuropathic pain model
Tumor necrosis factor receptor 1 induces interleukin-6 upregulation through NF-kappaB in a rat neuropathic pain model
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DOI：
10.1016/j.ejpain.2008.09.009
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发表时间：
2009-09-01
影响因子：
3.6
通讯作者：
Cho, Hee-Jung
中科院分区：
文献类型：
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作者：
Lee, Kyung-Min;Jeon, Sang-Min;Cho, Hee-Jung
周围神经损伤导致神经病理性疼痛，诱导白细胞介素6和肿瘤坏死因子α表达上调，并与肿瘤坏死因子受体1结合，在脊髓和背根节诱导核因子-kappaB和p38MAPK激活。我们研究了在坐骨神经慢性压迫损伤(CCI)大鼠中，TNFR1是否通过激活脊髓和背根节中的核因子-kappaB或p38MAPK来调节IL-6的表达。鞘内注射肿瘤坏死因子受体1反义寡核苷酸(ASO)可显著抑制CCI诱导的IKKS磷酸化、IKB-α降解和核转位。脊髓和背根节中核因子-kappaB的磷酸化和DNA结合活性、p38MAPK的激活以及IL-6mRNA和蛋白的表达。有趣的是，CCI显著增加了脊髓中ikkα和p65的磷酸化，而不是DRG。此外，NF-kappa B诱饵，而不是p38 MAPK抑制剂，SB203580降低了CCI诱导的脊髓和DRG中IL-6的表达。因此，这些结果表明，TNFR1通过核因子-kappaB而不是p38MAPK在脊髓和DRG中诱导IL-6上调和神经病理性疼痛，并且DRG中的NF-kappa B/IL-6通路对TNFR1的依赖程度可能低于脊髓通路。(C)2008年欧洲国际疼痛研究协会分会联合会。爱思唯尔有限公司出版。保留所有权利。
Peripheral nerve injury resulting in neuropathic pain induces the upregulation of interleukin (IL)-6 and tumor necrosis factor-alpha, which binds to tumor necrosis factor receptor 1 (TNFR1) and induces NF-kappa B and p38 MAPK activation in the spinal cord and dorsal root ganglia (DRG). We here investigated whether TNFR1 regulates IL-6 expression through NF-kappa B or p38 MAPK activations in the spinal cord and DRG in rats with chronic constriction injury (CCI) of the sciatic nerve. Intrathecal treatment with a TNFR1 antisense oligonucleotide (ASO) significantly inhibited CCI-elevated IKKs phosphorylation, IkB-alpha degradation, the nuclear translocation. phosphorylation, and DNA-binding activity of NF-kappa B, p38 MAPK activation, and IL-6 mRNA and protein expression in the spinal cord and DRG. Interestingly, CCI remarkably elevated IKK alpha and p65 phosphorylations in the spinal cord rather than in the DRG. In addition, NF-kappa B decoy, but not p38 MAPK inhibitor, SB203580 reduced CCI-elevated IL-6 expression in the spinal cord and DRG. Therefore, these data suggest that TNFR1 induces IL-6 upregulation and neuropathic pain through NF-kappa B, but not p38 MAPK activation in the spinal cord and DRG and that the NF-kappa B/IL-6 pathways in the DRG may be less dependent on TNFR1 than the spinal cord pathway. (C) 2008 European Federation of Chapters of the International Association for the Study of Pain. Published by Elsevier Ltd. All rights reserved.