Tanaka Masahito, Kikuchi Hitoshi, Ishizu Takaaki, Minohara Motozumi, Osoegawa Manabu, Motomura Kyoko, Tateishi Takahisa, Ohyagi Yasumasa, Kira Jun-ichi
Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
J Neuropathol Exp Neurol. 2006 Aug;65(8):816-25. doi: 10.1097/01.jnen.0000232025.84238.e1.
To investigate cytokine/chemokine changes in amyotrophic lateral sclerosis (ALS), we simultaneously measured 16 cytokine/chemokines (interleukin [IL]-1beta, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12 [p70], IL-13, IL-17, interferon-gamma, tumor necrosis factor-alpha, granulocyte colony stimulating factor [G-CSF], macrophage chemoattractant protein-1 [MCP-1], and macrophage inflammatory protein-1beta) in cerebrospinal fluid (CSF) and sera from 37 patients with sporadic ALS and 33 controls using a multiplexed fluorescent bead-based immunoassay. We also conducted immunohistochemical analyses from 8 autopsied ALS cases and 6 nonneurologic disease controls as well as cell culture analyses of relevant cytokines and their receptors. We found that concentrations of G-CSF and MCP-1 were significantly increased in ALS CSF compared with controls. In spinal cords, G-CSF was expressed in reactive astrocytes in ALS cases but not controls, whereas G-CSF receptor expression was significantly decreased in motor neurons of spinal cords from ALS cases. Biologically, G-CSF had a protective effect on the NSC34 cell line under conditions of both oxidative and nutritional stress. We suggested that G-CSF has potentially neuroprotective effects on motor neurons in ALS and that downregulation of its receptor might contribute to ALS pathogenesis. On the other hand, MCP-1 correlated with disease severity, which may aggravate motor neuron damage.
为了研究肌萎缩侧索硬化症（ALS）中细胞因子/趋化因子的变化，我们使用基于多重荧光微珠的免疫测定法，同时检测了37例散发性ALS患者和33例对照者脑脊液（CSF）和血清中的16种细胞因子/趋化因子（白细胞介素[IL]-1β、IL-2、IL-4、IL-5、IL-6、IL-7、IL-8、IL-10、IL-12[p70]、IL-13、IL-17、干扰素-γ、肿瘤坏死因子-α、粒细胞集落刺激因子[G-CSF]、巨噬细胞趋化蛋白-1[MCP-1]和巨噬细胞炎性蛋白-1β）。我们还对8例ALS尸检病例和6例非神经疾病对照进行了免疫组织化学分析，以及对相关细胞因子及其受体进行了细胞培养分析。我们发现，与对照组相比，ALS患者脑脊液中G-CSF和MCP-1的浓度显著升高。在脊髓中，G-CSF在ALS病例的反应性星形胶质细胞中表达，而在对照组中不表达，而ALS病例脊髓运动神经元中G-CSF受体的表达显著降低。从生物学角度来看，在氧化应激和营养应激条件下，G-CSF对NSC34细胞系具有保护作用。我们认为，G-CSF可能对ALS患者的运动神经元具有神经保护作用，其受体的下调可能有助于ALS的发病机制。另一方面，MCP-1与疾病严重程度相关，这可能会加重运动神经元损伤。
