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肿瘤坏死因子-α转化酶:眼部炎症性疾病的影响。

Tumor necrosis factor-alpha converting enzyme: Implications for ocular inflammatory diseases.

机构信息

Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, 301 University Blvd, Galveston, TX 77555, USA.

出版信息

Int J Biochem Cell Biol. 2010 Jul;42(7):1076-9. doi: 10.1016/j.biocel.2010.03.011. Epub 2010 Mar 18.

Abstract

Tumor necrosis factor-alpha (TNF-alpha) converting enzyme (TACE), a member of the family of metalloproteinase disintegrin proteins, is responsible for the conversion of inactive TNF-alpha precursor form to active mature form. TNF-alpha is a pleiotropic cytokine that contributes to cellular immunity and inflammatory response in wide range of inflammatory pathologies. Although a large number of studies indicate the use of TACE inhibitors, which prevents processing of TNF-alpha as potential therapeutic drugs for the treatment of inflammatory diseases including rheumatoid arthritis, Crohn's disease and cancer, very few studies indicate its use in ocular pathologies. It is still not clearly understood how the TACE-mediated shedding of cytokines and growth factors in various ocular tissues plays a critical role in the cytotoxic signals causing tissue dysfunction and damage leading to blindness. Regulation of TACE activity is likely to have wide implications for ocular immunology and inflammatory diseases. Specifically, since anti-TNF-alpha therapies have been used to prevent ocular inflammatory complications, the use of TACE inhibitors could be a novel therapeutic approach for ocular inflammatory diseases especially uveitis.

摘要

肿瘤坏死因子-α(TNF-α)转化酶(TACE)是金属蛋白酶解整合素蛋白家族的成员,负责将无活性的 TNF-α前体形式转化为活性成熟形式。TNF-α是一种多效细胞因子,有助于细胞免疫和广泛的炎症病理学中的炎症反应。尽管大量研究表明使用 TACE 抑制剂可防止 TNF-α的加工,将其作为治疗包括类风湿性关节炎、克罗恩病和癌症在内的炎症性疾病的潜在治疗药物,但很少有研究表明其在眼部疾病中的应用。目前尚不清楚 TACE 介导的各种眼部组织中细胞因子和生长因子的脱落如何在导致组织功能障碍和损伤导致失明的细胞毒性信号中发挥关键作用。TACE 活性的调节可能对眼部免疫学和炎症性疾病具有广泛的影响。具体而言,由于抗 TNF-α疗法已被用于预防眼部炎症并发症,因此使用 TACE 抑制剂可能是治疗眼部炎症性疾病(特别是葡萄膜炎)的一种新的治疗方法。

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