Intestinal Barrier Dysfunction, LPS Translocation, and Disease Development
Intestinal Barrier Dysfunction, LPS Translocation, and Disease Development
复制标题
DOI：
10.1210/jendso/bvz039
复制
发表时间：
2020-02-01
影响因子：
4.1
通讯作者：
Ghosh, Shobha
中科院分区：
文献类型：
--
作者：
Ghosh, Siddhartha S.;Wang, Jing;Ghosh, Shobha
肠屏障是复杂的，由多层组成，它为腔内容物向体循环的运输提供了物理和功能屏障。虽然上皮细胞层和外/内粘蛋白层构成物理屏障并且通常被称为肠屏障，但由上皮细胞产生的肠碱性磷酸酶（TAP）和由Panneth细胞分泌的抗菌蛋白代表功能屏障。虽然抗菌蛋白在宿主防御肠道微生物中发挥重要作用，但IAP通过催化活性/毒性脂质A部分的去磷酸化来解毒细菌内毒素脂多糖（LPS），从而防止局部炎症以及活性LPS易位到体循环中。循环LPS水平和多种疾病的发展之间的因果关系强调了详细检查与疾病发展相关的肠道屏障“层”变化的重要性，以及这种功能障碍如何通过有针对性的干预措施来减弱。为了开发改善肠道屏障功能的靶向治疗方法，必须深入了解肠道屏障本身，即屏障功能障碍导致疾病发展的潜在机制（例如，高循环LPS水平），在疾病条件下肠屏障功能的评估，以及如何有利地调节肠屏障的各个层以潜在地减弱相关疾病的发展。本文综述了肠屏障的组成及其评估和调制的屏障功能障碍相关疾病的潜在治疗的发展目前的知识。(C)内分泌学会2020年。
The intestinal barrier is complex and consists of multiple layers, and it provides a physical and functional barrier to the transport of luminal contents to systemic circulation. While the epithelial cell layer and the outer/inner mucin layer constitute the physical barrier and are often referred to as the intestinal barrier, intestinal alkaline phosphatase (TAP) produced by epithelial cells and antibacterial proteins secreted by Panneth cells represent the functional barrier. While antibacterial proteins play an important role in the host defense against gut microbes, IAP detoxifies bacterial endotoxin lipopolysaccharide (LPS) by catalyzing the dephosphorylation of the active/toxic Lipid A moiety, preventing local inflammation as well as the translocation of active LPS into systemic circulation. The causal relationship between circulating LPS levels and the development of multiple diseases underscores the importance of detailed examination of changes in the "layers" of the intestinal barrier associated with disease development and how this dysfunction can be attenuated by targeted interventions. To develop targeted therapies for improving intestinal barrier function, it is imperative to have a deeper understanding of the intestinal barrier itself, the mechanisms underlying the development of diseases due to barrier dysfunction (eg, high circulating LPS levels), the assessment of intestinal barrier function under diseased conditions, and of how individual layers of the intestinal barrier can be beneficially modulated to potentially attenuate the development of associated diseases. This review summarizes the current knowledge of the composition of the intestinal barrier and its assessment and modulation for the development of potential therapies for barrier dysfunction-associated diseases. (C) Endocrine Society 2020.