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.

Health benefits of resveratrol: Evidence from clinical studies

“…While a significant reduction in IL‐6 and alkaline phosphatase (ALP) was observed for the GE‐RES group, GE treatment alone could reduce only ALP after the first 6 months. A reduction in ALP levels is closely associated with a decrease in inflammatory conditions . Furthermore, the inflammatory cytokines, CCL3, IL‐1β, and TNF‐α, were all found to be significantly reduced in the peripheral blood mononuclear cells (PBMCs) of participants in both treatment groups.…”

“…A reduction in ALP levels is closely associated with a decrease in inflammatory conditions. 45,46 Furthermore, the inflammatory cytokines, CCL3, IL-1β, and TNF-α, were all found to be significantly reduced in the peripheral blood mononuclear cells (PBMCs) of participants in both treatment groups. Additionally, the modulation of inflammatory responses in both intervention groups were significantly correlated with inflammationrelated microRNAs (miRNAs) in PBMCs.…”

Effects of microwave processing conditions on microbial safety and antimicrobial proteins in bovine milk

“…The use of ALP as a method for pasteurization validation underappreciates its potential biological role. Although not many studies have evaluated the biological effects of milk ALP, intestinal ALP, which was shown to have similar substrate specificity than milk ALP (Morton, ), was shown to have a protective effect against intestinal and systemic inflammation by detoxifying lipopolysaccharide (Bates, Akerlund, Mittge, & Guillemin, ; Bilski et al, ). Treatment 8, for example, was shown to efficiently reduce pathogenic bacteria while preserving up to 3 times more ALP (1,095 mU/ml) than the conventional methods of pasteurization.…”

Biomimetic enzyme barrier for preventing intestine-derived LPS induced diseases

“…Of particular concern is the use of alkaline phosphatase (ALP) as they play an important role in gut barrier's function which contribute to the degradation of excessive LPS. [14][15][16] Although multiple researches of intravenous application of ALP in sepsis and septic shock has showed their value in preventing organ dysfunction, there is still no approach for enhancing barrier function and solving the pathogeny.…”