The contributing role of CD14 in toll-like receptor 4 dependent neuropathic pain.
The contributing role of CD14 in toll-like receptor 4 dependent neuropathic pain.
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DOI：
10.1016/j.neuroscience.2008.10.004
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发表时间：
2009-01-23
期刊：
影响因子：
3.3
通讯作者：
Deleo JA
中科院分区：
文献类型：
--
作者：
Cao L;Tanga FY;Deleo JA
我们先前已经证明，中枢神经系统(CNS)Toll样受体4(TLR4)在神经病理性疼痛的啮齿动物模型--脊神经L5横断术(L5Tx)中起着关键作用。TLR4是已知的天然免疫应答中的内毒素受体。本研究进一步探讨了内毒素-TLR4信号通路中的辅助分子CD14在L5Tx诱导的神经病理性疼痛中的作用。CD14基因敲除(KO)小鼠早在L5Tx后第1天就表现出明显的行为敏感性降低(机械痛觉过敏和热痛觉过敏)，表明CD14具有伤害性作用。通过流式细胞仪分析，我们观察到L5Tx后3天，同侧腰髓小胶质细胞表面CD14的表达显著增加，小胶质细胞的大小(通过前向散射(FSC))和颗粒(通过侧向散射(SSC))显著增加。此外，鞘内注射可溶性CD14在野生型(C3H/HEN)小鼠中诱导的机械超敏反应显著高于TLR4缺陷(C3H/HeJ)小鼠。综上所述，这些数据表明CD14在TLR4依赖的神经损伤诱导的神经病理性疼痛中起着重要作用。
We have previously demonstrated that central nervous system (CNS) toll-like receptor 4 (TLR4) plays a key role in the development of behavioral hypersensitivity in a rodent model of neuropathic pain, spinal nerve L5 transection (L5Tx). TLR4 is a well-known receptor for lipopolysaccharide (LPS) in innate immune responses. In the current study, we further investigated the role of CD14, an accessory molecule in the LPS-TLR4 signaling pathway, in the development of L5Tx-induced neuropathic pain. CD14 knockout (KO) mice displayed significantly decreased behavioral sensitivity (mechanical allodynia and thermal hyperalgesia) as early as day 1 post-L5Tx, indicating a nociceptive role of CD14. By flow cytometric analyses, we observed significantly elevated microglial surface CD14 expression in the ipsilateral lumbar spinal cord 3 days post-L5Tx, as well as remarkable increases in microglial size (via forward scatter (FSC)) and granularity (via side scatter (SSC)). Further, intrathecal injection of soluble CD14 induced significantly greater mechanical hypersensitivity in wild type (C3H/HeN) mice compared to TLR4-deficient (C3H/HeJ) mice. Together, these data demonstrate that CD14 plays a contributing role in TLR4-dependent nerve injury-induced neuropathic pain.
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影响因子：
6.2
作者：
Bettoni, Isabella;Comelli, Francesca;Costa, Barbara
通讯作者：
Costa, Barbara
影响因子：
--
作者：
Lacroix-Fralish, Michael L.;Tawfik, Vivianne L.;DeLeo, Joyce A.
通讯作者：
DeLeo, Joyce A.
影响因子：
5.8
作者：
Landmann, R;Müller, B;Zimmerli, W
通讯作者：
Zimmerli, W
影响因子：
3.3
作者：
LaCroix-Fralish, ML;Tawfik, VL;DeLeo, JA
通讯作者：
DeLeo, JA
影响因子：
3.3
作者：
Lutterotti, Andreas;Kuenz, Bettina;Reindl, Markus
通讯作者：
Reindl, Markus