Neuronal IL-17 receptor upregulates TRPV4 but not TRPV1 receptors in DRG neurons and mediates mechanical but not thermal hyperalgesia
Neuronal IL-17 receptor upregulates TRPV4 but not TRPV1 receptors in DRG neurons and mediates mechanical but not thermal hyperalgesia
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DOI：
10.1016/j.mcn.2012.11.006
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发表时间：
2013-01-01
影响因子：
3.5
通讯作者：
Schaible, Hans-Georg
中科院分区：
文献类型：
--
作者：
von Banchet, Gisela Segond;Boettger, Michael K.;Schaible, Hans-Georg
除了促炎细胞因子肿瘤坏死因子- α、白细胞介素-6和白细胞介素-1 β外，细胞因子白细胞介素-17 （IL-17）被认为是类风湿关节炎等自身免疫性疾病的重要介质。由于肿瘤坏死因子- α和白细胞介素-1 β有可能影响瞬时受体电位香草酸样蛋白1 （TRPV1）等转导分子在背根神经节（DRG）神经元中的表达，从而导致疼痛，我们在本研究中探讨IL-17A是否激活DRG神经元并影响TRPV1的表达。IL-17A受体在背根神经节（DRG）的大部分神经元以及培养的DRG神经元中可见。长期暴露于IL-17A后，分离和培养的大鼠DRG神经元细胞外调节激酶（ERK）和核因子κ B （NF κ B）显著上调。长期暴露于IL-17A的神经元并没有上调TRPV1的表达。然而，我们发现瞬时受体电位香草蛋白4 （TRPV4）明显上调，这被认为是机械性痛觉过敏的候选转导分子。il - 17a缺失小鼠在足部注射酶酶多糖后，机械性痛觉过敏比野生型小鼠减轻，而热痛觉过敏没有减轻。因此，这些数据表明，IL-17在机械性痛觉过敏中的特殊作用，他们认为这种作用与TRPV4的激活和上调有关。(c) 2012 Elsevier Inc.版权所有。
In addition to the proinflammatory cytokines tumor necrosis factor-alpha, interleukin-6 and interleukin-1 beta, the cytokine interleukin-17 (IL-17) is considered an important mediator of autoimmune diseases such as rheumatoid arthritis. Because tumor necrosis factor-alpha and interleukin-1 beta have the potential to influence the expression of transduction molecules such as transient receptor potential vanilloid 1 (TRPV1) in dorsal root ganglion (DRG) neurons and thus to contribute to pain we explored in the present study whether IL-17A activates DRG neurons and influences the expression of TRPV1. The IL-17A receptor was visualized in most neurons in dorsal root ganglion (DRG) sections as well as in cultured DRG neurons. Upon long-term exposure to IL-17A, isolated and cultured rat DRG neurons showed a significant upregulation of extracellular-regulated kinase (ERK) and nuclear factor kappa B (NF kappa B). Long-term exposure of neurons to IL-17A did not upregulate the expression of TRPV1. However, we found a pronounced upregulation of transient receptor potential vanilloid 4 (TRPV4) which is considered a candidate transduction molecule for mechanical hyperalgesia. Upon the injection of zymosan into the paw, IL-17A-deficient mice showed less mechanical hyperalgesia than wild type mice but thermal hyperalgesia was not attenuated in IL-17A-deficient mice. These data show, therefore, a particular role of IL-17 in mechanical hyperalgesia, and they suggest that this effect is linked to an activation and upregulation of TRPV4. (c) 2012 Elsevier Inc. All rights reserved.