Role of Intestinal Alkaline Phosphatase in Innate Immunity

Abstract

Intestinal alkaline phosphatase (IAP) is a multi-functional protein that has been demonstrated to primarily protect the gut. The role of IAP in maintaining intestinal homeostasis is underscored by the observation that IAP expression is defective in many gastrointestinal-related disorders such as inflammatory bowel disease IBD, necrotizing enterocolitis, and metabolic syndrome and that exogenous IAP supplementation improves the outcomes associated with these disorders. Additionally, studies using transgenic IAP-knock out (IAP-KO) mouse models further support the importance of the defensive role of IAP in the intestine. Supplementation of exogenous IAP and cellular overexpression of IAP have also been used in vitro to dissect out the downstream mechanisms of this protein in mammalian cell lines. Some of the innate immune functions of IAP include lipopolysaccharide (LPS) detoxification, protection of gut barrier integrity, regulation of gut microbial communities and its anti-inflammatory roles. A novel function of IAP recently identified is the induction of autophagy. Due to its critical role in the gut physiology and its excellent safety profile, IAP has been used in phase 2a clinical trials for treating conditions such as sepsis-associated acute kidney injury. Many excellent reviews discuss the role of IAP in physiology and pathophysiology and here we extend these to include recent updates on this important host defense protein and discuss its role in innate immunity via its effects on bacteria as well as on host cells. We will also discuss the relationship between IAP and autophagy and how these two pathways may act in concert to protect the gut.

Modulating phenylalanine metabolism by L. acidophilus alleviates alcohol-related liver disease through enhancing intestinal barrier function

“…IAP has been found mediating interactions between microorganism communities and the host. IAP dephosphorylates LPS and other pathogen-associated molecular patterns, reducing local intestinal inflammation [ 35 ] and helping maintain gut barrier function [ 29 , 36 ]. IAP supplementation has been reported to be able to ameliorate experimental colitis [ 37 ], reverse metabolic syndrome [ 38 ], prevent liver fibrosis [ 21 ], and attenuate alcohol-induced hepatosteatosis [ 20 ].…”

Comparative analysis for immune response of coelomic fluid from coelom and polian vesicle in Apostichopus japonicus to Vibrio splendidus infection

“…In this study, the activity of ACP showed an increased trend in the coelom with a peak at 48 hpi, while it exhibited a decreased pattern except a significant elevation at 48 hpi, suggesting ACP in polian vesicle had a slight and delayed response to pathogenic infection. AKP has been demonstrated to play a role in innate immune response by lipopolysaccharide (LPS) detoxification, anti-inflammatory function and induction of autophagy in many studies [ 35 , 36 ]. In our result, the AKP activity both in the coelomic and polian vesicle fluid shared a consistently increasing levels after V. splendidus challenge, revealing an important role of AKP in coelomic and polian vesicle fluid.…”

Intestinal alkaline phosphatase (IAP, IAP Enhancer) attenuates intestinal inflammation and alleviates insulin resistance

“…We also showed that the IAP enhancer could still reach the duodenum after it was exposed to gastric acid. IAP dephosphorylates LPS ( 60 ), ATP ( 11 ), and UDP ( 61 ). However, the effect of IAP on dephosphorylation has not been reported in the pH range (pH 5–8) in the small intestine of humans and other nucleoside triphosphates.…”