ArticleGut2004
Increased epithelial uptake of protein antigens in the ileum of Crohn's disease mediated by tumour necrosis factor alpha.
Article in Gut, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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Who cites it
62 citing papers in PubMed, 160 citations in OpenAlex.
- Natural Bioactive Compounds Targeting Gut Barrier Integrity and Metabolic Endotoxemia in Cardiometabolic Disease: Mechanistic Insights and Translational Perspectives.Molecules (Basel, Switzerland) · 2026Review
- 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
- Exploring the intricate link between gut microbiota dysbiosis and the aging process: implications for age-related diseases.Gut pathogens · 2025Review
- Variability in intestinal drug metabolizing enzymes and transporters in Crohn's disease and potential impact on oral drug absorption.British journal of clinical pharmacology · 2025Article
- The Effect of Inflammatory Bowel Disease and Irritable Bowel Syndrome on Pravastatin Oral Bioavailability: In vivo and in silico evaluation using bottom-up wbPBPK modeling.AAPS PharmSciTech · 2024Article
- Exploring the therapeutic potential of cinnamoyl derivatives in attenuating inflammation in lipopolysaccharide-induced Caco-2 cells.Future medicinal chemistry · 2024Article
- Intestinal Barrier Function and Neurodegenerative Disease.CNS & neurological disorders drug targets · 2024Review
- Restore Intestinal Barrier Integrity: An Approach for Inflammatory Bowel Disease Therapy.Journal of inflammation research · 2024Review
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- Uptake ofInternational journal of molecular sciences · 2023Article
- Insights of Endocytosis Signaling in Health and Disease.International journal of molecular sciences · 2023Review
- Assessing Cellular and Transcriptional Diversity of Ileal Mucosa Among Treatment-Naïve and Treated Crohn's Disease.Inflammatory bowel diseases · 2023Article
- Harnessing murine models of Crohn's disease ileitis to advance concepts of pathophysiology and treatment.Mucosal immunology · 2022Review
- Regulation of Intestinal Inflammation by Soybean and Soy-Derived Compounds.Foods (Basel, Switzerland) · 2021Review
- The Role of Intestinal Permeability in Gastrointestinal Disorders and Current Methods of Evaluation.Frontiers in nutrition · 2021Review
- Clinical relevance of intestinal barrier dysfunction in common gastrointestinal diseases.World journal of gastrointestinal pathophysiology · 2020Review
- Review
- Article
- Enhanced E. coli LF82 Translocation through the Follicle-associated Epithelium in Crohn's Disease is Dependent on Long Polar Fimbriae and CEACAM6 expression, and Increases Paracellular Permeability.Journal of Crohn's & colitis · 2020Article
- Article
2 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
aimsThe exact nature of the epithelial barrier defect in Crohn's disease remains to be elucidated. Previously we showed increased permeability to proteins in ileal Crohn's disease. Our aims were to study if this barrier defect (a) involves endocytotic uptake of antigens and (b) is related to low grade inflammation not detectable by histology.
methodsMacroscopically normal segments of distal ileum of Crohn's disease patients (n = 10) were subgrouped into non-inflamed (histologically unaffected) and slightly inflamed tissues and studied in Ussing chambers, with normal ileal specimens from colon cancer patients (n = 9) as controls. Endocytotic uptake into enterocytes of the protein antigen horseradish peroxidase was assessed by measuring the area of horseradish peroxidase containing endosomes in electron photomicrographs. Mucosal tumour necrosis factor alpha (TNF-alpha) mRNA was quantified using real time polymerase chain reaction. For comparison, the effects of low doses of TNF-alpha on endosomal uptake of horseradish peroxidase were studied in cultured T84 cells grown on filter supports.
resultsThe area of horseradish peroxidase containing endosomes was increased (p<0.001) in enterocytes of non-inflamed ileum of Crohn's disease (2.8 (0.7) mum(2)/300 mum(2)) compared with control ileum (0.6 (0.06)). In non-inflamed mucosa, a significant association between endosomal uptake and mucosal expression of TNF-alpha mRNA (p = 0.03) was found. Low concentrations of TNF-alpha (0.25-1.0 ng/ml) enhanced the endosomal uptake of horseradish peroxidase in polarised T84 cells, without affecting transepithelial electrical resistance.
conclusionsOur findings suggest increased endosomal uptake of antigens in ileal Crohn's disease that may be mediated by TNF-alpha. These data highlight the transcellular route of antigen uptake in barrier dysfunction and implicate the interaction between epithelial cells and the innate immune system in the development of mucosal inflammation.
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