C.A.I.R. Institute, The Safdié AIDS and Immunology Research Center, The Mina & Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan 52900, Israel.
C.A.I.R. Institute, The Safdié AIDS and Immunology Research Center, The Mina & Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan 52900, Israel.
Autoimmun Rev. 2014 Dec;13(12):1230-5. doi: 10.1016/j.autrev.2014.08.003. Epub 2014 Aug 19.
Tellurium is a rare element, which has been regarded as a non-essential trace element despite its relative abundance in the human body. The chemistry of tellurium supports a plethora of activities, but its biochemistry is not clearly established to date. The small tellurium(IV) compound, ammonium trichloro (dioxoethylene-o,o')tellurate (AS101) developed and initially investigated by us, is currently being evaluated in Phase II clinical trials in psoriasis patients. AS101 is the first tellurium compound to be tested for clinical efficacy. This compound is a potent immunomodulator both in vitro and in vivo with a variety of potential therapeutic applications. The present review will focus on the immunomodulatory properties of AS101, and specifically, its effects in mitigating autoimmune diseases. AS101 has several activities that act on the immune system, including: 1) its ability to reduce IL-17 levels and to inhibit the function of Th17 cells; 2) its specific unique redox-modulating activities enabling the inhibition of specific leukocyte integrins such as α4β1 and α4β7, that are pivotal for diapedesis of macrophages and CD4(+) T inflammatory/auto-reactive cells into the autoimmune tissues; and 3) its ability to enhance the activity of regulatory T cells (Treg). These activities coupled with its excellent safety profile suggest that AS101 may be a promising candidate for the management of autoimmune diseases.
碲是一种稀有元素,尽管它在人体中的相对丰度较高,但一直被认为是非必需的微量元素。碲的化学性质支持着大量的活动,但迄今为止,其生物化学性质尚未得到明确的确定。我们开发并初步研究的小碲(IV)化合物,三氯(二氧乙烯-o,o') 碲酸铵(AS101),目前正在银屑病患者的 II 期临床试验中进行评估。AS101 是第一个经过临床疗效测试的碲化合物。该化合物在体外和体内均具有很强的免疫调节作用,具有多种潜在的治疗应用。本综述将重点介绍 AS101 的免疫调节特性,特别是其在减轻自身免疫性疾病方面的作用。AS101 具有多种作用于免疫系统的活性,包括:1)降低 IL-17 水平并抑制 Th17 细胞功能;2)其独特的特定氧化还原调节活性,能够抑制特定白细胞整合素,如α4β1 和α4β7,这些整合素对于巨噬细胞和 CD4(+)T 炎症/自身反应性细胞向自身免疫组织的渗出至关重要;3)增强调节性 T 细胞(Treg)的活性。这些活性以及其出色的安全性特征表明,AS101 可能是治疗自身免疫性疾病的有希望的候选药物。