ArticleThe American journal of gastroenterology2014
Novel role of the serine protease inhibitor elafin in gluten-related disorders.
Article in The American journal of gastroenterology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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33 citing papers in PubMed, 69 citations in OpenAlex.
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- Immune cell dynamics and mechanisms of epithelial injury in celiac disease.Frontiers in immunology · 2026Review
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- Is There a Future Without Gluten Restrictions for Celiac Patients? Update on Current Treatments.Nutrients · 2025Review
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- Effect of ischemia-reperfusion injury on elafin levels in rat liver.Ulusal travma ve acil cerrahi dergisi = Turkish journal of trauma & emergency surgery : TJTES · 2024Article
- Expression of Elafin and CD200 as Immune Checkpoint Molecules Involved in Celiac Disease.International journal of molecular sciences · 2024Article
- Elafin and its precursor trappin-2: What is their therapeutic potential for intestinal diseases?British journal of pharmacology · 2023Review
- Gut microbial β-glucuronidases regulate host luminal proteases and are depleted in irritable bowel syndrome.Nature microbiology · 2022Article
- The double-edged sword of gut bacteria in celiac disease and implications for therapeutic potential.Mucosal immunology · 2022Review
- Fungal Proteases as Emerging Biocatalysts to Meet the Current Challenges and Recent Developments in Biomedical Therapies: An Updated Review.Journal of fungi (Basel, Switzerland) · 2022Review
- UEG Week 2020 Oral Presentations.United European gastroenterology journal · 2020Article
- Elafin inhibits obesity, hyperglycemia, and liver steatosis in high-fat diet-treated male mice.Scientific reports · 2020Article
- Serine proteases as luminal mediators of intestinal barrier dysfunction and symptom severity in IBS.Gut · 2020Article
- Duodenal bacterial proteolytic activity determines sensitivity to dietary antigen through protease-activated receptor-2.Nature communications · 2019Article
- The Contribution of Gut Barrier Changes to Multiple Sclerosis Pathophysiology.Frontiers in immunology · 2019Review
- Mechanisms by which gut microorganisms influence food sensitivities.Nature reviews. Gastroenterology & hepatology · 2019Review
- Autoimmune phenotypes in schizophrenia reveal novel treatment targets.Pharmacology & therapeutics · 2018Review
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18 authors at 7 institutions in 4 countries.
Funding
Abstract
objectivesElafin, an endogenous serine protease inhibitor, modulates colonic inflammation. We investigated the role of elafin in celiac disease (CD) using human small intestinal tissues and in vitro assays of gliadin deamidation. We also investigated the potential beneficial effects of elafin in a mouse model of gluten sensitivity.
methodsEpithelial elafin expression in the small intestine of patients with active CD, treated CD, and controls without CD was determined by immunofluorescence. Interaction of elafin with human tissue transglutaminase-2 (TG-2) was investigated in vitro. The 33-mer peptide, a highly immunogenic gliadin peptide, was incubated with TG-2 and elafin at different concentrations. The degree of deamidation of the 33-mer peptide was analyzed by liquid chromatography-mass spectrometry. Elafin was delivered to the intestine of gluten-sensitive mice using a recombinant Lactococcus lactis vector. Small intestinal barrier function, inflammation, proteolytic activity, and zonula occludens-1 (ZO-1) expression were assessed.
resultsElafin expression in the small intestinal epithelium was lower in patients with active CD compared with control patients. In vitro, elafin significantly slowed the kinetics of the deamidation of the 33-mer peptide to its more immunogenic form. Treatment of gluten-sensitive mice with elafin delivered by the L. lactis vector normalized inflammation, improved permeability, and maintained ZO-1 expression.
conclusionsThe decreased elafin expression in the small intestine of patients with active CD, the reduction of 33-mer peptide deamidation by elafin, coupled to the barrier enhancing and anti-inflammatory effects observed in gluten-sensitive mice, suggest that this molecule may have pathophysiological and therapeutic importance in gluten-related disorders.
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