胆红素免疫调节活性的可能分子机制。

International Journal of Medicinal Chemistry Pub Date : 2013-01-01 Epub Date: 2013-04-09 DOI:10.1155/2013/467383
Hideto Isogai, Noriaki Hirayama
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引用次数: 6

摘要

胆红素是哺乳动物血红素降解的内源性产物。胆红素长期以来被认为是一种需要排出的细胞毒性废物。然而,越来越多的证据表明胆红素具有多种生物活性。特别是,最近的研究表明,胆红素应该是一些自身免疫性疾病的保护因素,如类风湿关节炎、多发性硬化症和系统性红斑狼疮。由于这些自身免疫性疾病与特定类型的人白细胞抗原(HLA)密切相关,我们假设胆红素可能与HLA分子的抗原肽结合槽结合并发挥其免疫抑制作用。为了验证这一假说,我们开展了胆红素与HLA相关分子的理论对接研究。计算机研究清楚地表明,胆红素可能与自身免疫性疾病相关HLA分子的抗原肽结合槽具有显著的亲和力。结合的胆红素可能阻断抗原肽的结合,将其呈递给T细胞受体,导致自身免疫反应的抑制。基于这一假设,将开展自身免疫性疾病的新药发现研究。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

A possible molecular mechanism of immunomodulatory activity of bilirubin.

A possible molecular mechanism of immunomodulatory activity of bilirubin.

A possible molecular mechanism of immunomodulatory activity of bilirubin.

A possible molecular mechanism of immunomodulatory activity of bilirubin.

Bilirubin is an endogenous product of heme degradation in mammals. Bilirubin has long been considered as a cytotoxic waste product that needs to be excreted. However, increasing evidence suggests that bilirubin possesses multiple biological activities. In particular, recent studies have shown that bilirubin should be a protective factor for several autoimmune diseases such as rheumatoid arthritis, multiple sclerosis, and systemic lupus erythematosus. Since these autoimmune diseases are closely associated with specific types of human leukocyte antigens (HLAs), we have hypothesized that bilirubin might bind to the antigenic peptide-binding groove of the HLA molecules and exert its immunosuppressive actions. In order to evaluate the hypothesis, theoretical docking studies between bilirubin and the relevant HLA molecules have been undertaken. The in silico studies have clearly shown that bilirubin may bind to the antigenic peptide-binding groove of the HLA molecules relevant to the autoimmune diseases with significant affinity. The bound bilirubin may block the binding of antigenic peptides to be presented to T cell receptors and lead to suppression of the autoimmune responses. Based on this hypothesis new drug discovery research for autoimmune diseases will be conducted.

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期刊介绍: International Journal of Medicinal Chemistry is a peer-reviewed, Open Access journal that publishes original research articles as well as review articles in all areas of chemistry associated with drug discovery, design, and synthesis. International Journal of Medicinal Chemistry is a peer-reviewed, Open Access journal that publishes original research articles as well as review articles in all areas of chemistry associated with drug discovery, design, and synthesis.
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