The Role of Intestinal Alkaline Phosphatase in Inflammatory Disorders of Gastrointestinal Tract

Abstract

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.

Figure 1

Hypothetical model depicting the mechanism by which a brush border enzyme intestinal alkaline phosphatase (IAP) affects the intestinal microbiota, the release of bacterial LPS-induced inflammation, and the luminal content of ATP inhibiting the commensal bacteria of different origin. Under inflammation, the proinflammatory cytokines can inhibit the content and activity of protective IAP. The IAP can dephosphorylate bacterial LPS which leads to LPS detoxification, thus preventing downstream activation of immunocytes and the subsequent inflammatory responses. The IAP can inhibit luminal ATP by the mechanism involving the ATP dephosphorylation. This enzyme was found to exert an inhibitory effect on the growth and survival of a wide spectrum of bacteria and to prevent bacteria translocation from intestinal lumen into bloodstream. The mechanisms illustrated in this figure which are described in the text were inspired by [8, 9] cited in this review.