ArticleThe Journal of pharmacology and experimental therapeutics2012
Interferon-γ activates transglutaminase 2 via a phosphatidylinositol-3-kinase-dependent pathway: implications for celiac sprue therapy.
Article in The Journal of pharmacology and experimental therapeutics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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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.
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Who cites it
19 citing papers in PubMed, 34 citations in OpenAlex.
- Transcriptomic analysis of intestine following administration of a transglutaminase 2 inhibitor to prevent gluten-induced intestinal damage in celiac disease.Nature immunology · 2024Trial
- Aberrant expression of transglutaminase 2 in pancreas and thymus of NOD mice underscores the importance of deamidation in neoantigen generation.Frontiers in endocrinology · 2022Article
- Assessment ofAnimals : an open access journal from MDPI · 2021Article
- Interplay Between Gluten, HLA, Innate and Adaptive Immunity Orchestrates the Development of Coeliac Disease.Frontiers in immunology · 2021Review
- Dietary Gluten and Neurodegeneration: A Case for Preclinical Studies.International journal of molecular sciences · 2020Review
- Structures of Human Transglutaminase 2: Finding Clues for Interference in Cross-linking Mediated Activity.International journal of molecular sciences · 2020Review
- Lipid profile, atherogenic indices, and their relationship with epicardial fat thickness and carotid intima-media thickness in celiac disease.Northern clinics of Istanbul · 2019Article
- Pharmacologic inhibition of the enzymatic effects of tissue transglutaminase reduces cardiac fibrosis and attenuates cardiomyocyte hypertrophy following pressure overload.Journal of molecular and cellular cardiology · 2018Article
- T Cells in Celiac Disease.Journal of immunology (Baltimore, Md. : 1950) · 2017Review
- Expression of Transglutaminase in Foreskin of Children with Balanitis Xerotica Obliterans.International journal of molecular sciences · 2016Article
- An unprecedented dual antagonist and agonist of human Transglutaminase 2.Bioorganic & medicinal chemistry letters · 2015Article
- PI3kα and STAT1 Interplay Regulates Human Mesenchymal Stem Cell Immune Polarization.Stem cells (Dayton, Ohio) · 2015Article
- The effects of reduced gluten barley diet on humoral and cell-mediated systemic immune responses of gluten-sensitive rhesus macaques.Nutrients · 2015Article
- Coeliac Disease - New Pathophysiological Findings and Their Implications for Therapy.Viszeralmedizin · 2014Review
- Novel mechanism of cytokine-induced disruption of epithelial barriers: Janus kinase and protein kinase D-dependent downregulation of junction protein expression.Tissue barriers · 2013Article
- Gluten-sensitive enteropathy coincides with decreased capability of intestinal T cells to secrete IL-17 and IL-22 in a macaque model for celiac disease.Clinical immunology (Orlando, Fla.) · 2013Article
- Selective inhibition of extracellular thioredoxin by asymmetric disulfides.Journal of medicinal chemistry · 2013Article
- Thioredoxin is involved in endothelial cell extracellular transglutaminase 2 activation mediated by celiac disease patient IgA.PloS one · 2013Article
- Role of transglutaminase 2 in celiac disease pathogenesis.Seminars in immunopathology · 2012Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The mechanism for activation of extracellular transglutaminase 2 (TG2) in the small intestine remains a fundamental mystery in our understanding of celiac sprue pathogenesis. Using the T84 human enterocytic cell line, we show that interferon-γ (IFN-γ), the predominant cytokine secreted by gluten-reactive T cells in the celiac intestine, activates extracellular TG2 in a dose-dependent manner. IFN-γ mediated activation of TG2 requires phosphatidylinositol-3-kinase (PI3K) activity, but is uninfluenced by a number of other kinases reported to be active in T84 cells. Pharmacological inhibition of PI3K in the presence of IFN-γ prevents TG2 activation as well as the previously characterized increase in transepithelial permeability. Our findings therefore establish PI3K as an attractive target for celiac sprue therapy, a possibility that is underscored by the encouraging safety profiles of several PI3K inhibitors undergoing human clinical trials.
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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.