Sayer Ji
Founder of GreenMedInfo.com

Subscribe to our informative Newsletter & get Nature's Evidence-Based Pharmacy

Our newsletter serves 500,000 with essential news, research & healthy tips, daily.

500+ pages of Natural Medicine Alternatives and Information.

Abstract Title:

Gliadin induces an increase in intestinal permeability and zonulin release by binding to the chemokine receptor CXCR3.

Abstract Source:

Gastroenterology. 2008 Jul;135(1):194-204.e3. Epub 2008 Mar 21. PMID: 18485912

Abstract Author(s):

Karen M Lammers, Ruliang Lu, Julie Brownley, Bao Lu, Craig Gerard, Karen Thomas, Prasad Rallabhandi, Terez Shea-Donohue, Amir Tamiz, Sefik Alkan, Sarah Netzel-Arnett, Toni Antalis, Stefanie N Vogel, Alessio Fasano

Article Affiliation:

Mucosal Biology Research Center, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.

Abstract:

BACKGROUND&AIMS: Celiac disease is an immune-mediated enteropathy triggered by gliadin, a component of the grain protein gluten. Gliadin induces an MyD88-dependent zonulin release that leads to increased intestinal permeability, a postulated early element in the pathogenesis of celiac disease. We aimed to establish the molecular basis of gliadin interaction with intestinal mucosa leading to intestinal barrier impairment. METHODS: Alpha-gliadin affinity column was loaded with intestinal mucosal membrane lysates to identify the putative gliadin-binding moiety. In vitro experiments with chemokine receptor CXCR3 transfectants were performed to confirm binding of gliadin and/or 26 overlapping 20mer alpha-gliadin synthetic peptides to the receptor. CXCR3 protein and gene expression were studied in intestinal epithelial cell lines and human biopsy specimens. Gliadin-CXCR3 interaction was further analyzed by immunofluorescence microscopy, laser capture microscopy, real-time reverse-transcription polymerase chain reaction, and immunoprecipitation/Western blot analysis. Ex vivo experiments were performed using C57BL/6 wild-type and CXCR3(-/-) mouse small intestines to measure intestinal permeability and zonulin release. RESULTS: Affinity column and colocalization experiments showed that gliadin binds to CXCR3 and that at least 2 alpha-gliadin 20mer synthetic peptides are involved in this binding. CXCR3 is expressed in mouse and human intestinal epithelia and lamina propria. Mucosal CXCR3 expression was elevated in active celiac disease but returned to baseline levels following implementation of a gluten-free diet. Gliadin induced physical association between CXCR3 and MyD88 in enterocytes. Gliadin increased zonulin release and intestinal permeability in wild-type but not CXCR3(-/-) mouse small intestine. CONCLUSIONS: Gliadin binds to CXCR3 and leads to MyD88-dependent zonulin release and increased intestinal permeability.

Study Type : In Vitro Study
Additional Links
Additional Keywords : Zonulin : CK(15) : AC(5)
Problem Substances : Gliadin : CK(819) : AC(116)

Print Options


Key Research Topics

Sayer Ji
Founder of GreenMedInfo.com

Subscribe to our informative Newsletter & get Nature's Evidence-Based Pharmacy

Our newsletter serves 500,000 with essential news, research & healthy tips, daily.

500+ pages of Natural Medicine Alternatives and Information.

This website is for information purposes only. By providing the information contained herein we are not diagnosing, treating, curing, mitigating, or preventing any type of disease or medical condition. Before beginning any type of natural, integrative or conventional treatment regimen, it is advisable to seek the advice of a licensed healthcare professional.

© Copyright 2008-2019 GreenMedInfo.com, Journal Articles copyright of original owners, MeSH copyright NLM.