Bilski Jan, Mazur-Bialy Agnieszka, Wojcik Dagmara, Zahradnik-Bilska Janina, Brzozowski Bartosz, Magierowski Marcin, Mach Tomasz, Magierowska Katarzyna, Brzozowski Tomasz
Department of Ergonomics and Exercise Physiology, Faculty of Health Sciences, Jagiellonian University Medical College, Cracow, Poland.
Department of Physiology, Faculty of Medicine, Jagiellonian University Medical College, Cracow, Poland.
Mediators Inflamm. 2017;2017:9074601. doi: 10.1155/2017/9074601. Epub 2017 Feb 21.
Over the past few years, the role of intestinal alkaline phosphatase (IAP) as a crucial mucosal defence factor essential for maintaining gut homeostasis has been established. IAP is an important apical brush border enzyme expressed throughout the gastrointestinal tract and secreted both into the intestinal lumen and into the bloodstream. IAP exerts its effects through dephosphorylation of proinflammatory molecules including lipopolysaccharide (LPS), flagellin, and adenosine triphosphate (ATP) released from cells during stressful events. Diminished activity of IAP could increase the risk of disease through changes in the microbiome, intestinal inflammation, and intestinal permeability. Exogenous IAP exerts a protective effect against intestinal and systemic inflammation in a variety of diseases and represents a potential therapeutic agent in diseases driven by gut barrier dysfunction such as IBD. The intestinal protective mechanisms are impaired in IBD patients due to lower synthesis and activity of endogenous IAP, but the pathomechanism of this enzyme deficiency remains unclear. IAP has been safely administered to humans and the human recombinant form of IAP has been developed. This review was designed to provide an update in recent research on the involvement of IAP in intestinal inflammatory processes with focus on IBD in experimental animal models and human patients.
在过去几年中,肠碱性磷酸酶(IAP)作为维持肠道稳态所必需的关键黏膜防御因子的作用已得到确立。IAP是一种重要的顶端刷状缘酶,在整个胃肠道中表达,并分泌到肠腔和血液中。IAP通过对促炎分子进行去磷酸化发挥作用,这些促炎分子包括在应激事件期间从细胞释放的脂多糖(LPS)、鞭毛蛋白和三磷酸腺苷(ATP)。IAP活性降低可能通过微生物群变化、肠道炎症和肠道通透性改变增加疾病风险。外源性IAP对多种疾病中的肠道和全身炎症具有保护作用,并且在由肠道屏障功能障碍驱动的疾病(如炎症性肠病)中代表一种潜在的治疗剂。由于内源性IAP的合成和活性降低,炎症性肠病患者的肠道保护机制受损,但这种酶缺乏的发病机制仍不清楚。IAP已被安全地应用于人体,并且已开发出IAP的重组人形式。本综述旨在提供关于IAP参与肠道炎症过程的最新研究进展,重点关注实验动物模型和人类患者中的炎症性肠病。