ArticleClinical and experimental immunology2012
Transglutaminase 2 expression is enhanced synergistically by interferon-γ and tumour necrosis factor-α in human small intestine.
Article in Clinical and experimental immunology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 51 citations in OpenAlex.
- Review
- Crosstalk between inflammation and autophagy in CeD organoids.Scientific reports · 2026Article
- Pulmonary-Intestinal Axis: Shared Genetic Basis and Mediating Factors Identified Through Multi-Omics Analysis.International journal of chronic obstructive pulmonary disease · 2026Article
- Protective Effects Proanthocyanidin Nanoliposome Freeze-Dried Powder on Oxidative Injury in a p31-43 Induced Celiac Disease Cell Model.Food science & nutrition · 2025Article
- Investigating the shared genetic architecture between obesity and depression: a large-scale genomewide cross-trait analysis.Frontiers in endocrinology · 2025Article
- Identifying common genetic etiologies between iridocyclitis and related immune-mediated diseases.Frontiers in immunology · 2025Article
- Identifying Common Genetic Etiologies Between Inflammatory Bowel Disease and Related Immune-Mediated Diseases.Biomedicines · 2024Article
- Shared genetic architecture between COVID-19 and irritable bowel syndrome: a large-scale genome-wide cross-trait analysis.Frontiers in immunology · 2024Article
- Coexistence of apoptosis, pyroptosis, and necroptosis pathways in celiac disease.Clinical and experimental immunology · 2023Article
- Functional implications of the CpG island methylation in the pathogenesis of celiac disease.Molecular biology reports · 2022Review
- Benefits of Polyphenols and Methylxanthines from Cocoa Beans on Dietary Metabolic Disorders.Foods (Basel, Switzerland) · 2021Review
- The Multifaceted Role of HSF1 in Pathophysiology: Focus on Its Interplay with TG2.International journal of molecular sciences · 2021Review
- Transglutaminase 2 moderates the expansion of mouse abdominal aortic aneurysms.JVS-vascular science · 2021Article
- Moonlighting Proteins Are Important Players in Cancer Immunology.Frontiers in immunology · 2020Review
- Article
- Differential Expression of Tissue Transglutaminase Splice Variants in Peripheral Blood Mononuclear Cells of Primary Progressive Multiple Sclerosis Patients.Medical sciences (Basel, Switzerland) · 2018Article
- The skin protective effects of compound K, a metabolite of ginsenoside Rb1 from Panax ginseng.Journal of ginseng research · 2018Article
- Monocyte-derived tissue transglutaminase in multiple sclerosis patients: reflecting an anti-inflammatory status and function of the cells?Journal of neuroinflammation · 2017Article
- New Insights into the Pathogenesis of Celiac Disease.Frontiers in medicine · 2017Review
- Transglutaminase is a Critical Link Between Inflammation and Hypertension.Journal of the American Heart Association · 2016Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Transglutaminase 2 (TG2) is expressed ubiquitously, has multiple physiological functions and has also been associated with inflammatory diseases, neurodegenerative disorders, autoimmunity and cancer. In particular, TG2 is expressed in small intestine mucosa where it is up-regulated in active coeliac disease (CD). The aim of this work was to investigate the induction of TG2 expression by proinflammatory cytokines [interleukin (IL)-1, IL-6, tumour necrosis factor (TNF)-α, interferon (IFN)-γ and IL-15] and the signalling pathways involved, in human epithelial and monocytic cells and in intestinal tissue from controls and untreated CD patients. Here we report that IFN-γ was the most potent inducer of TG2 expression in the small intestinal mucosa and in four [Caco-2, HT-29, Calu-6 and human acute monocytic leukaemia cell line (THP-1)] of five cell lines tested. The combination of TNF-α and IFN-γ produced a strong synergistic effect. The use of selective inhibitors of signalling pathways revealed that induction of TG2 by IFN-γ was mediated by phosphoinositide 3-kinase (PI3K), while c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) were required for TNF-α activation. Quantitative polymerase chain reaction (PCR), flow cytometry and Western blot analysis showed that TG2 expression was blocked completely when stimulation by either TNF-α or IFN-γ was performed in the presence of nuclear factor (NF)-κB inhibitors (sulphasalazine and BAY-117082). TG2 was up-regulated substantially by TNF-α and IFN-γ in intestinal mucosa in untreated CD compared with controls. This study shows that IFN-γ, a dominant cytokine in intestinal mucosa in active CD, is the most potent inducer of TG2, and synergism with TNF-α may contribute to exacerbate the pathogenic mechanism of CD. Selective inhibition of signalling pathways may be of therapeutic benefit.
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