Heparanase upregulates Th2 cytokines, ameliorating experimental autoimmune encephalitis
Heparanase upregulates Th2 cytokines, ameliorating experimental autoimmune encephalitis
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DOI：
10.1016/j.molimm.2010.03.014
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发表时间：
2010-06-01
影响因子：
3.6
通讯作者：
Vlodavsky, Israel
中科院分区：
文献类型：
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作者：
Bitan, Menachem;Weiss, Lola;Vlodavsky, Israel
乙酰肝素酶是一种内切β-D-葡萄糖醛酸酶，可切割硫酸乙酰肝素（HS）糖链。该酶促进细胞粘附、迁移和侵袭，并在癌症转移、血管生成和炎症中起重要作用。本研究的重点是乙酰肝素酶参与自身免疫，应用小鼠实验性自身免疫性脑炎（EAE）模型，T细胞依赖性疾病，经常用于调查多发性硬化症（MS）的病理生理。腹腔注射重组乙酰肝素酶以剂量依赖性方式改善了该疾病的临床体征。在体外和体内研究表明，乙酰肝素酶抑制有丝分裂原诱导的脾细胞增殖和混合淋巴细胞反应（MLR），通过调节其细胞因子的库，由IL-4，IL-6和IL-10的水平显着增加，并在IL-12和TNF-α的平行下降表示。用活性的、潜伏的或点突变的无活性乙酰肝素酶获得类似的结果，表明观察到的抑制作用归因于乙酰肝素酶蛋白的非酶活性。我们认为，乙酰肝素酶诱导上调Th 2细胞因子，从而抑制EAE的炎性病变。(C)2010爱思唯尔有限公司版权所有。
Heparanase is an endo-beta-D-glucuronidase that cleaves heparan sulfate (HS) saccharide chains. The enzyme promotes cell adhesion, migration and invasion and plays a significant role in cancer metastasis, angiogenesis and inflammation. The present study focuses on the involvement of heparanase in autoimmunity, applying the murine experimental autoimmune encephalitis (EAE) model, a T-cell dependent disease often used to investigate the pathophysiology of multiple sclerosis (MS). Intraperitoneal administration of recombinant heparanase ameliorated, in a dose dependent manner, the clinical signs of the disease. In vitro and in vivo studies revealed that heparanase inhibited mitogen induced splenocyte proliferation and mixed lymphocyte reaction (MLR) through modulation of their repertoire of cytokines indicated by a marked increase in the levels of IL-4, IL-6 and IL-10, and a parallel decrease in IL-12 and TNF-alpha. Similar results were obtained with active, latent, or point mutated inactive heparanase, indicating that the observed inhibitory effect is attributed to a non-enzymatic activity of the heparanase protein. We suggest that heparanase induces upregulation of Th2 cytokines, resulting in inhibition of the inflammatory lesion of EAE. (C) 2010 Elsevier Ltd. All rights reserved.