IL-17A is increased in the serum and in spinal cord CD8 and mast cells of ALS patients.
IL-17A is increased in the serum and in spinal cord CD8 and mast cells of ALS patients.
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DOI：
10.1186/1742-2094-7-76
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发表时间：
2010-11-09
影响因子：
9.3
通讯作者：
Wiedau-Pazos M
中科院分区：
文献类型：
--
作者：
Fiala M;Chattopadhay M;La Cava A;Tse E;Liu G;Lourenco E;Eskin A;Liu PT;Magpantay L;Tse S;Mahanian M;Weitzman R;Tong J;Nguyen C;Cho T;Koo P;Sayre J;Martinez-Maza O;Rosenthal MJ;Wiedau-Pazos M
炎症对神经退行性疾病的贡献越来越多地被认识到，但炎症在散发性肌萎缩侧索硬化症（sALS）中的作用还没有得到很好的理解，并且没有动物模型可用。我们使用酶联免疫吸附试验（ELISA）来测量ALS患者（n = 32; 28散发性ALS（sALS）和4个家族性ALS（fALS））和对照组（n = 14; 10名健康受试者和4名自身免疫性疾病）血清中的细胞因子白细胞介素-17 A（IL-17 A）。IL-17 A血清浓度在sALS患者中为5767 ± 2700 pg/ml（平均值土SEM），在fALS患者中为937 ± 927 pg/ml，相比之下，在没有自身免疫性疾病的对照受试者中为7 ± 2 pg/ml（通过Mann-Whitney检验，ALS患者相对于对照受试者p = 0.008）。64%的患者和无对照受试者具有IL-17 A血清浓度> 50 pg/ml（通过Fisher精确检验，ALS患者相对于健康受试者p = 0.003）。sALS（n = 8）的脊髓被白细胞介素-1 β（IL-1β）和肿瘤坏死因子-α阳性巨噬细胞（与神经元共定位）、IL-17 A阳性CD 8细胞和IL-17 A阳性肥大细胞浸润，而对照受试者（n = 4）则没有。用野生型超氧化物歧化酶-1（SOD-1）的聚集形式处理的单核细胞显示细胞因子IL-1β、白细胞介素-6（IL-6）和白细胞介素-23（IL-23）的诱导，其可能负责IL-17 A的诱导。在对28，869个基因的微阵列分析中，与对照组相比，突变型超氧化物歧化酶-1刺激外周血单核细胞诱导患者单核细胞中白细胞介素-1 α（IL-1α）、IL-6、CCL 20、基质金属肽酶1和组织因子途径抑制剂2的转录增加4倍，而抗炎细胞因子白细胞介素-10（IL-10）在对照受试者的单核细胞中增加。聚集在sALS神经元中的野生型SOD-1可在单个核细胞中诱导引起sALS脊髓慢性炎症的细胞因子，特别是IL-6和IL-17 A，从而损伤神经元。慢性炎症的免疫调节可能是sALS的新途径。
The contribution of inflammation to neurodegenerative diseases is increasingly recognized, but the role of inflammation in sporadic amyotrophic lateral sclerosis (sALS) is not well understood and no animal model is available. We used enzyme-linked immunosorbent assays (ELISAs) to measure the cytokine interleukin-17A (IL-17A) in the serum of ALS patients (n = 32; 28 sporadic ALS (sALS) and 4 familial ALS (fALS)) and control subjects (n = 14; 10 healthy subjects and 4 with autoimmune disorders). IL-17A serum concentrations were 5767 ± 2700 pg/ml (mean ± SEM) in sALS patients and 937 ± 927 pg/ml in fALS patients in comparison to 7 ± 2 pg/ml in control subjects without autoimmune disorders (p = 0.008 ALS patients vs. control subjects by Mann-Whitney test). Sixty-four percent of patients and no control subjects had IL-17A serum concentrations > 50 pg/ml (p = 0.003 ALS patients vs. healthy subjects by Fisher's exact test). The spinal cords of sALS (n = 8), but not control subjects (n = 4), were infiltrated by interleukin-1β- (IL-1β-), and tumor necrosis factor-α-positive macrophages (co-localizing with neurons), IL-17A-positive CD8 cells, and IL-17A-positive mast cells. Mononuclear cells treated with aggregated forms of wild type superoxide dismutase-1 (SOD-1) showed induction of the cytokines IL-1β, interleukin-6 (IL-6), and interleukin-23 (IL-23) that may be responsible for induction of IL-17A. In a microarray analysis of 28,869 genes, stimulation of peripheral blood mononuclear cells by mutant superoxide dismutase-1 induced four-fold higher transcripts of interleukin-1α (IL-1α), IL-6, CCL20, matrix metallopeptidase 1, and tissue factor pathway inhibitor 2 in mononuclear cells of patients as compared to controls, whereas the anti-inflammatory cytokine interleukin-10 (IL-10) was increased in mononuclear cells of control subjects. Aggregated wild type SOD-1 in sALS neurons could induce in mononuclear cells the cytokines inducing chronic inflammation in sALS spinal cord, in particular IL-6 and IL-17A, damaging neurons. Immune modulation of chronic inflammation may be a new approach to sALS.
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影响因子：
30.5
作者：
Acosta-Rodriguez, Eva V.;Napolitani, Giorgio;Sallusto, Federica
通讯作者：
Sallusto, Federica
影响因子：
64.8
作者：
Bettelli, E;Carrier, YJ;Kuchroo, VK
通讯作者：
Kuchroo, VK
影响因子：
11.2
作者：
Henkel, JS;Engelhardt, JI;Appel, SH
通讯作者：
Appel, SH
DOI：
10.1046/j.1365-2362.2002.00994.x
发表时间：
2002-05-01
影响因子：
5.5
作者：
Fiala, M;Liu, QN;Vinters, HV
通讯作者：
Vinters, HV
影响因子：
25
作者：
Bosco, Daryl A.;Morfini, Gerardo;Karabacak, N. Murat;Song, Yuyu;Gros-Louis, Francois;Pasinelli, Piera;Goolsby, Holly;Fontaine, Benjamin A.;Lemay, Nathan;McKenna-Yasek, Diane;Frosch, Matthew P.;Agar, Jeffrey N.;Julien, Jean-Pierre;Brady, Scott T.;Brown, Robert H., Jr.
通讯作者：
Brown, Robert H., Jr.