Protective effect of an elastase inhibitor in a neuromyelitis optica-like disease driven by a peptide of myelin oligodendroglial glycoprotein
Protective effect of an elastase inhibitor in a neuromyelitis optica-like disease driven by a peptide of myelin oligodendroglial glycoprotein
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DOI：
10.1177/1352458512440060
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发表时间：
2012-04-01
影响因子：
5.8
通讯作者：
Axtell, Robert C.
中科院分区：
文献类型：
--
作者：
Herges, Katja;de Jong, Brigit A.;Axtell, Robert C.
背景资料：与多发性硬化相反，视神经肌萎缩症（NMO）的病理学包括沿沿着脊髓以及视神经的广泛长度的粒细胞浸润。此外，IFN-β治疗可抑制NMO。我们最近发现，实验性自身免疫性脑脊髓炎（EAE）诱导的Th 17细胞是加剧IFN-β，在与Th 1的治疗减弱symptoms.Objective：这项研究表明，NMO和Th 17 EAE之间的相似性和中性粒细胞如何介导的病理在Th 17 diseases.Methods：血液生物标志物的水平在NMO进行了评估Luminex和ELISA。IFN-β对中性粒细胞的影响通过培养测定和免疫荧光法进行评估。EAE是由髓磷脂特异性Th 1或Th 17细胞的转移和治疗西维来司钠水合物，中性粒细胞弹性蛋白酶inhibitors.Results：我们显示Th 17细胞因子，粒细胞趋化因子，1型干扰素和中性粒细胞弹性蛋白酶升高的患者与明确的NMO。在培养中，我们发现IFN-β刺激中性粒细胞释放中性粒细胞弹性蛋白酶。在Th 17型EAE中，我们证实了Th 1型EAE中不存在的视神经和脊髓中的嗜中性粒细胞浸润。Sivelestat阻断中性粒细胞弹性蛋白酶对Th 17型EAE.Conclusions：Th 17型EAE与NMO的相似性表明该模型代表了NMO的几个方面。中性粒细胞在Th 17-EAE和NMO的病理学中是关键的，因此中性粒细胞弹性蛋白酶的阻断是治疗NMO的有希望的靶点。
Background: The pathology of neuromyelitis optica (NMO), in contrast to multiple sclerosis, comprises granulocyte infiltrates along extensive lengths of spinal cord, as well as optic nerve. Furthermore, IFN-beta treatment worsens NMO. We recently found that experimental autoimmune encephalomyelitis (EAE) induced with Th17 cells is exacerbated by IFN-beta, in contrast to disease induced with Th1 where treatment attenuated symptoms.Objective: This study demonstrates the similarities between NMO and Th17 EAE and how neutrophils mediate pathology in Th17 disease.Methods: Levels of blood biomarkers in NMO were assessed by Luminex and ELISA. Effects of IFN-beta on neutrophils were assessed by culture assays and immunofluorescence. EAE was induced by transfer of myelin-specific Th1 or Th17 cells and treated with Sivelestat sodium hydrate, a neutrophil elastase inhibitor.Results: We show Th17 cytokines, granulocyte chemokines, type 1 interferon and neutrophil elastase are elevated in patients with definitive NMO. In culture, we find that IFN-beta stimulates neutrophils to release neutrophil elastase. In Th17 EAE, we demonstrate neutrophilic infiltration in the optic nerve and spinal cord which was not present in Th1 EAE. Blockade of neutrophil elastase with Sivelestat had efficacy in Th17 EAE but not Th1 EAE.Conclusions: The similarities between Th17 EAE and NMO indicate that this model represents several aspects of NMO. Neutrophils are critical in the pathologies of both Th17-EAE and NMO, and therefore blockade of neutrophil elastase is a promising target in treating NMO.