Genetic evidence for an essential role of neuronally expressed IL-6 signal transducer gp130 in the induction and maintenance of experimentally induced mechanical hypersensitivity in vivo and in vitro.
Genetic evidence for an essential role of neuronally expressed IL-6 signal transducer gp130 in the induction and maintenance of experimentally induced mechanical hypersensitivity in vivo and in vitro.
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DOI：
10.1186/1744-8069-7-73
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发表时间：
2011-09-27
期刊：
影响因子：
3.3
通讯作者：
Kress M
中科院分区：
文献类型：
--
作者：
Quarta S;Vogl C;Constantin CE;Üçeyler N;Sommer C;Kress M
压痛和机械性超敏是恶性肿瘤、炎症和神经病的主要症状。促炎细胞因子白介素6(IL-6)在所有三种病理过程中都有因果关系。IL-6不仅调节先天免疫和炎症，还引起伤害性感受器敏化和痛觉过敏。一般情况下，在包括免疫细胞和感觉神经元在内的大多数细胞类型中，IL-6与可溶性μ受体亚基结合，后者与膜结合的IL-6信号转导蛋白gp130异构化。在本研究中，我们使用条件基因敲除策略来研究在C伤害性感受器中表达的信号转导蛋白gp130在机械超敏反应的产生和维持中的重要性。通过实验性肿瘤使伤害性感受器对机械刺激敏感，这种伤害性感受器敏感化在对照组小鼠病理的后期阶段被保留。然而，在通过实验性肿瘤表达伤害性感受器机械超敏反应的Nav1.8中有条件删除gp130的小鼠中，神经损伤或炎症恢复在维持期没有保留，伤害性感受器显示出与未经治疗的小鼠相当的正常机械阈值。总之，这些结果表明，IL-6信号转导蛋白gp130是与癌症、炎症和神经损伤相关的长期机械超敏反应的伤害性感受器的基本先决条件。
Tenderness and mechanical allodynia are key symptoms of malignant tumor, inflammation and neuropathy. The proinflammatory cytokine interleukin-6 (IL-6) is causally involved in all three pathologies. IL-6 not only regulates innate immunity and inflammation but also causes nociceptor sensitization and hyperalgesia. In general and in most cell types including immune cells and sensory neurons, IL-6 binds soluble μ receptor subunits which heteromerizes with membrane bound IL-6 signal transducer gp130. In the present study, we used a conditional knock-out strategy to investigate the importance of signal transducer gp130 expressed in C nociceptors for the generation and maintenance of mechanical hypersensitivity. Nociceptors were sensitized to mechanical stimuli by experimental tumor and this nociceptor sensitization was preserved at later stages of the pathology in control mice. However, in mice with a conditional deletion of gp130 in Nav1.8 expressing nociceptors mechanical hypersensitivity by experimental tumor, nerve injury or inflammation recovery was not preserved in the maintenance phase and nociceptors exhibited normal mechanical thresholds comparable to untreated mice. Together, the results argue for IL-6 signal transducer gp130 as an essential prerequisite in nociceptors for long-term mechanical hypersensitivity associated with cancer, inflammation and nerve injury.
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创伤后，通过上调白介素（IL）6和IL-6受体的表达来加速小鼠的神经再生。
影响因子：
15.3
作者：
Hirota, H;Kiyama, H;Kishimoto, T;Taga, T
通讯作者：
Taga, T
影响因子：
5.8
作者：
Bennett, Gary J.
通讯作者：
Bennett, Gary J.
影响因子：
9.8
作者：
Delaney, A.;Fleetwood-Walker, S. M.;Fallon, M.
通讯作者：
Fallon, M.
影响因子：
46.9
作者：
Fischer, M;Goldschmitt, J;RoseJohn, S
通讯作者：
RoseJohn, S
DOI：
10.1073/pnas.0409225102
发表时间：
2005-02-01
影响因子：
11.1
作者：
Cunha, TM;Verri, WA;Ferreira, SH
通讯作者：
Ferreira, SH