ArticleGastroenterology2008
Gliadin induces an increase in intestinal permeability and zonulin release by binding to the chemokine receptor CXCR3.
Article in Gastroenterology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 3 registered trials, which are not on this map. Cited by 243 papers, 3 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
The Effect of a Gluten Free Diet on the Permeability of the Blood Brain Barrier in Patients With Clinically Isolated Syndrome Measured by Dynamic Contrast Enhanced Magnetic Resonance Imaging
Crossover Trial of Purified Gluten and Whole Wheat (Gluten With Amylase-trypsin Inhibitors) as Triggers of Gastrointestinal Symptoms in Patients With Irritable Bowel Syndrome
The Investigation of Nutritional Status, Intestinal Permeability and Quality of Life in People With Celiac Disease
Who cites it
243 citing papers in PubMed, 3 syntheses or guidelines pooled it, 528 citations in OpenAlex.
- Gluten-Free and Gluten-Restricted Diets in Multiple Sclerosis: A Systematic Review of Disease Activity and Patient-Reported Outcomes.Nutrients · 2026Pooled it
- Prognostic role of elevated VEGF in sepsis: A systematic review and meta-analysis.Frontiers in physiology · 2022Pooled it
- Gliadin-Specific T-Cells Mobilized in the Peripheral Blood of Coeliac Patients by Short Oral Gluten Challenge: Clinical Applications.Nutrients · 2015Pooled it
- The Effect of Gluten Free Diet on Components of Metabolic Syndrome: A Randomized Clinical TrialAsian Pacific journal of cancer prevention : APJCP · 2018Trial
- Larazotide acetate for persistent symptoms of celiac disease despite a gluten-free diet: a randomized controlled trial.Gastroenterology · 2015Trial
- Diet, gut microbiome, and type 1 diabetes: from risk to translational opportunity.Gut microbes · 2026Review
- Celiac Disease and the Nervous System: A Comprehensive Overview of Neurological Manifestations and Underlying Mechanisms.Neuromolecular medicine · 2026Review
- KetoFLEX 12/3 Diet and Cognitive Health: A Precision-Nutrition Perspective on Mechanisms, Emerging Evidence, and Future Directions.Nutrients · 2026Review
- Serum Zonulin and Chitinase (CHI3L1) as Biomarkers of Intestinal Permeability and Disease Activity in Pediatric Celiac Disease.Children (Basel, Switzerland) · 2026Article
- Pro-Inflammatory Cytokines as Core Mediators of Colonic Epithelial Barrier Dysfunction: Roles of TNF-α, IFN-γ, IL-1β, and IL-6.International journal of molecular sciences · 2026Review
- Assessing Skin Barrier Integrity: A Comparative Study Using Transepidermal Water Loss, Electrical Impedance Spectroscopy and Corneometry.Contact dermatitis · 2026Article
- Elimination of Autism Symptoms Using the Specific Carbohydrate Diet: Literature Review and Case Report.Integrative medicine (Encinitas, Calif.) · 2026Review
- Article
- Intestinal permeability and the zonulin pathway: tight junctions, mucosal immunity, dietary modulators and clinical relevance.Frontiers in nutrition · 2026Review
- Gluten intake and its possible relationship with pain, skin symptoms, and mental health in the Spanish population: an observational study.Frontiers in nutrition · 2026Article
- Innate immune dysregulation in celiac disease and refractory celiac disease: mechanisms, management and emerging therapies.Frontiers in immunology · 2026Review
- Gut barrier-microbiota crosstalk in sepsis: from pathogenesis to potential therapies.Frontiers in immunology · 2026Review
- From gluten to therapeutics: molecular mechanisms of celiac disease and emerging alternatives to the gluten-free diet.Frontiers in pharmacology · 2026Review
- Bifidobacteria and Celiac Disease: Mechanisms of Probiotic Action in Reducing Gluten-Induced Cytotoxicity and Inflammation.Molecular nutrition & food research · 2025Review
- Investigating Non-celiac Wheat Sensitivity: A Comprehensive Review of Pathophysiology Underlying Clinical Implications.Clinical reviews in allergy & immunology · 2025Review
183 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 2 institutions in 1 country.
Funding
Abstract
BACKGROUND &
aimsCeliac 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.
methodsAlpha-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.
resultsAffinity 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.
conclusionsGliadin binds to CXCR3 and leads to MyD88-dependent zonulin release and increased intestinal permeability.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.