ArticleJournal of clinical immunology2013
Are transglutaminase 2 inhibitors able to reduce gliadin-induced toxicity related to celiac disease? A proof-of-concept study.
Article in Journal of clinical immunology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
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Who cites it
20 citing papers in PubMed, 50 citations in OpenAlex.
- Oxaliplatin-induced testicular toxicity is associated with transglutaminase-4 upregulation, hormonal dysregulation, and inflammatory responses.Journal of applied biomedicine · 2026Article
- Role of Regulatory T Cells and Transglutaminase 2 Inhibitors in Celiac Disease: A Systematic Review.Cureus · 2025Review
- Celiac Disease-Narrative Review on Progress in Celiac Disease.Foods (Basel, Switzerland) · 2025Review
- Gluten-Free Diet Adherence Evaluation in Adults with Long-Standing Celiac Disease.Foods (Basel, Switzerland) · 2024Article
- Coeliac Disease in Children-A Clinical Review Including Novel Treatment Agents.Medicina (Kaunas, Lithuania) · 2024Review
- Inhibition of Transglutaminase 2 as a Therapeutic Strategy in Celiac Disease-In Vitro Studies in Intestinal Cells and Duodenal Biopsies.International journal of molecular sciences · 2023Article
- The TGM2 inhibitor cysteamine hydrochloride does not impact corneal epithelial and stromal wound healing in vitro and in vivo.Experimental eye research · 2023Article
- Type 2 Transglutaminase in Coeliac Disease: A Key Player in Pathogenesis, Diagnosis and Therapy.International journal of molecular sciences · 2022Review
- Interplay between Type 2 Transglutaminase (TG2), Gliadin Peptide 31-43 and Anti-TG2 Antibodies in Celiac Disease.International journal of molecular sciences · 2020Review
- Celiac Disease and Non-celiac Wheat Sensitivity: State of Art of Non-dietary Therapies.Frontiers in nutrition · 2020Review
- MAGI2 Gene Region and Celiac Disease.Frontiers in nutrition · 2019Article
- Novel Nondietary Therapies for Celiac Disease.Cellular and molecular gastroenterology and hepatology · 2019Review
- Extra-Intestinal Manifestation of Celiac Disease in Children.Nutrients · 2018Review
- The gliadin peptide 31-43 exacerbates kainate neurotoxicity in epilepsy models.Scientific reports · 2017Article
- Calcium glycerophosphate preserves transepithelial integrity in the Caco-2 model of intestinal transport.World journal of gastroenterology · 2015Article
- Non-dietary methods in the treatment of celiac disease.Przeglad gastroenterologiczny · 2015Review
- Biological functionalities of transglutaminase 2 and the possibility of its compensation by other members of the transglutaminase family.TheScientificWorldJournal · 2014Review
- Latest in vitro and in vivo models of celiac disease.Expert opinion on drug discovery · 2013Review
- Celiac disease: a challenging disease for pharmaceutical scientists.Pharmaceutical research · 2013Article
- Novel targets for drug discovery in celiac disease.Indian journal of pharmacologyReview
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeCeliac disease is an autoimmune-mediated enteropathy characterized by adaptive and innate immune responses to dietary gluten in wheat, rye and barley in genetically susceptible individuals. Gluten-derived gliadin peptides are deamidated by transglutaminase 2 (TG2), leading to an immune response in the small-intestinal mucosa. TG2 inhibitors have therefore been suggested as putative drugs for celiac disease. In this proof-of-concept study we investigated whether two TG2 inhibitors, cell-impermeable R281 and cell-permeable R283, can prevent the toxic effects of gliadin in vitro and ex vivo.
methodsIntestinal epithelial Caco-2 cells were treated with peptic-tryptic-digested gliadin (PT-gliadin) with or without TG2 inhibitors and thereafter direct toxic effects (transepithelial resistance, cytoskeletal rearrangement, junction protein expression and phoshorylation of extracellular-signal-regulated kinase 1/2) were determined. In an organ culture of celiac-patient-derived small-intestinal biopsies we measured secretion of TG2-autoantibodies into the culture medium and the densities of CD25- and interleukin (IL) 15-positive cells, forkhead box P3 (FOXP3)-positive regulatory T cells (Tregs) and Ki-67-positive proliferating crypt cells.
resultsBoth TG2 inhibitors evinced protective effects against gliadin-induced detrimental effects in Caco-2 cells but the cell-impermeable R281 seemed slightly more potent. In addition, TG2 inhibitor R281 modified the gluten-induced increase in CD25- and IL15-positive cells, Tregs and crypt cell proliferation, but had no effect on antibody secretion in celiac-patient-derived biopsies.
conclusionsOur results suggest that TG2 inhibitors are able to reduce certain gliadin-induced effects related to responses in vitro and ex vivo.
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Registered trials
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