Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran; Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran; Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Shahid Beheshti Universtity of Medical Sciences, Tehran, Iran.
Pharmacol Res. 2018 Mar;129:204-215. doi: 10.1016/j.phrs.2017.11.017. Epub 2017 Nov 16.
Inflammatory bowel disease (IBD) is the chronic inflammation of the gastrointestinal tract. Recently, studies of the interplay between the adaptive and innate immune responses have provided a better understanding of the immunopathogenesis of inflammatory disorders such as IBD, as well as identification of novel targets for more potent interventions. Toll-like receptors (TLRs) are a class of proteins that play a significant role in the innate immune system and are involved in inflammatory processes. Activation of TLR signal transduction pathways lead to the induction of numerous genes that function in host defense, including those for inflammatory cytokines, chemokines, and antigen presenting molecules. It was proposed that TLR mutations and dysregulation are major contributing factors to the predisposition and susceptibility to IBD. Thus, modulating TLRs represent an innovative immunotherapeutic approach in IBD therapy. This article outlines the role of TLRs in IBD, focusing on both animal and human studies; the role of TLR-targeted agonists or antagonists as potential therapeutic agents in the different stages of the disease is discussed.
炎症性肠病(IBD)是胃肠道的慢性炎症。最近,对适应性和先天免疫反应之间相互作用的研究,为炎症性疾病(如 IBD)的免疫发病机制提供了更好的理解,并确定了更有效的干预措施的新靶点。Toll 样受体(TLR)是一类在先天免疫系统中发挥重要作用的蛋白质,参与炎症过程。TLR 信号转导途径的激活导致许多宿主防御功能基因的诱导,包括炎症细胞因子、趋化因子和抗原呈递分子的基因。有人提出,TLR 突变和失调是 IBD 易感性和易患性的主要因素。因此,调节 TLR 是 IBD 治疗中的一种创新免疫治疗方法。本文概述了 TLR 在 IBD 中的作用,重点介绍了动物和人类研究;讨论了 TLR 靶向激动剂或拮抗剂作为疾病不同阶段潜在治疗药物的作用。