Elevated levels of IFNγ and LIGHT in the spinal cord of patients with sporadic amyotrophic lateral sclerosis
Elevated levels of IFNγ and LIGHT in the spinal cord of patients with sporadic amyotrophic lateral sclerosis
复制标题
DOI：
10.1111/j.1468-1331.2011.03623.x
复制
发表时间：
2012-05-01
影响因子：
5.1
通讯作者：
Raoul, C.
中科院分区：
文献类型：
--
作者：
Aebischer, J.;Moumen, A.;Raoul, C.
背景资料：肌萎缩侧索硬化症（amyotrophiclateralsclerosis，ALS）是一种由上下运动神经元逐渐丧失引起的瘫痪性和致死性神经退行性疾病。ALS实验模型有令人信服的证据表明，神经炎症积极促进运动神经元损伤。我们最近提出干扰素γ（IFN？），一种有效的促炎性细胞因子，通过其配体LIGHT引发光毒素β受体（LT-β R）的激活来诱导运动神经元死亡。在这里，我们探讨这种非细胞自主机制在人类ALS.Methods的相关性：IFN γ，LIGHT和LT-β R的水平和表达模式进行了研究，通过Western blot和免疫组化分析在脊髓中的散发性ALS.Results患者：我们观察到显着增加的IFN γ在人类ALS脊髓的水平相比，对照病例。我们发现，大腹角神经元以及胶质细胞的免疫反应IFN γ在散发性ALS脊髓。我们进一步观察到LIGHT和LT-β R在ALS和对照病例中主要由运动神经元表达，而LT-β R水平在ALS和对照病例之间保持恒定，LIGHT水平在人ALS脊髓中增加。这些在散发性ALS病例中的发现与ALS实验模型中的观察结果一致，提出IFN γ触发的LIGHT/LT-β R介导的死亡途径可能有助于人类ALS发病机制。
Background: Amyotrophic lateral sclerosis (ALS) is a paralytic and fatal neurodegenerative disorder caused by the gradual loss of both upper and lower motoneurons. There is compelling evidence from ALS experimental models that neuroinflammation actively contributes to motoneuron damage. We recently proposed that interferon gamma (IFN?), a potent proinflammatory cytokine, induces motoneuron death by eliciting the activation of the lymphotoxin beta receptor (LT-beta R) through its ligand LIGHT. Here, we explore the pertinence of this non-cell-autonomous mechanism in human ALS.Methods: The levels and expression pattern of IFN gamma, LIGHT, and LT-beta R were investigated by Western blot and immunohistochemical analysis in spinal cord of patients with sporadic ALS.Results: We observed significant increased levels of IFN gamma in human ALS spinal cords compared to control cases. We found that large ventral horn neurons as well as glial cells were immunoreactive for IFN gamma in sporadic ALS spinal cord. We further observed that LIGHT and LT-beta R were expressed mainly by motoneurons in both ALS and control cases, and while LT-beta R levels remained constant between ALS and control cases, LIGHT levels were increased in human ALS spinal cords.Conclusion: These findings in sporadic ALS cases, which are consistent with the observation made in ALS experimental models, propose that the IFN gamma-triggered LIGHT/LT-beta R-mediated death pathway may contribute to human ALS pathogenesis.