Antiinflammatory and immunosuppressive activity of sialostatin L, a salivary cystatin from the tick Ixodes scapularis

Antiinflammatory and immunosuppressive activity of sialostatin L, a salivary cystatin from the tick Ixodes scapularis
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DOI:
10.1074/jbc.m513010200
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发表时间:
2006-09-08
影响因子:
4.8
通讯作者:
Ribeiro, Jose M. C.
Ribeiro, Jose M. C.
中科院分区:
生物学2区
文献类型:
--
作者:
Kotsyfakis, Michalis;Sa-Nunes, Anderson;Ribeiro, Jose M. C.

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在这里,我们报告的能力,蜱肩胛硬蜱,莱姆病在美国的主要载体,积极和具体地影响主机的蛋白水解活性的感染部位,通过释放半胱氨酸蛋白酶抑制剂的组成部分,其唾液。半胱氨酸蛋白酶抑制剂在唾液中的存在进行了生物化学和免疫学验证。我们将该蛋白命名为唾液抑素L,因为它对组织蛋白酶L具有抑制作用。我们还表明,它所靶向的蛋白酶尽管数量有限,但在细胞外和细胞内环境中发生的蛋白水解级联反应中发挥着重要作用。其结果是,sialostatin L显示出抑制作用并抑制细胞毒性T淋巴细胞的增殖。除了解开另一个组成部分占蜱唾液的特性,有助于喂养成功和病原体传播,我们描述了一种新的工具,用于研究木瓜蛋白酶样蛋白酶在各种生物现象和蛋白质中的作用,具有许多潜在的制药应用。
Here we report the ability of the tick Ixodes scapularis, the main vector of Lyme disease in the United States, to actively and specifically affect the host proteolytic activity in the sites of infestation through the release of a cystatin constituent of its saliva. The cystatin presence in the saliva was verified both biochemically and immunologically. We named the protein sialostatin L because of its inhibitory action against cathepsin L. We also show that the proteases it targets, although limited in number, have a prominent role in the proteolytic cascades that take place in the extracellular and intracellular environment. As a result, sialostatin L displays an antiinflammatory role and inhibits proliferation of cytotoxic T lymphocytes. Beyond unraveling another component accounting for the properties of tick saliva, contributing to feeding success and pathogen transmission, we describe a novel tool for studying the role of papain-like proteases in diverse biologic phenomena and a protein with numerous potential pharmaceutical applications.