ArticlePloS one2013
Pepsin digest of wheat gliadin fraction increases production of IL-1β via TLR4/MyD88/TRIF/MAPK/NF-κB signaling pathway and an NLRP3 inflammasome activation.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
56 citing papers in PubMed, 1 synthesis or guideline pooled it, 112 citations in OpenAlex.
- Pooled it
- Lactic Acid Bacteria with Probiotic Potential Regulating Macrophages: Mechanisms, Regulatory Features, and Clinical Applications.Probiotics and antimicrobial proteins · 2026Review
- From gluten to therapeutics: molecular mechanisms of celiac disease and emerging alternatives to the gluten-free diet.Frontiers in pharmacology · 2026Review
- Association of NLRC4 inflammasome targeting Caspase1 to regulate monocyte pyroptosis involved in ankylosing spondylitis pathogenesis.Clinical rheumatology · 2025Article
- Celiac Disease-Narrative Review on Progress in Celiac Disease.Foods (Basel, Switzerland) · 2025Review
- Identifying Key Biomarkers in Celiac Disease through Analysis of Microarray Data.Journal of medical signals and sensors · 2025Article
- Dietary Components in the Pathogenesis and Prevention of Type 1 Diabetes in Children.Hormone research in paediatrics · 2025Review
- Inflammasomes in Intestinal Disease: Mechanisms of Activation and Therapeutic Strategies.International journal of molecular sciences · 2024Review
- The Role of Gluten in the Development of Autoimmune Thyroid Diseases: A Narrative Review.International journal of endocrinology and metabolism · 2024Review
- Changes upon the gluten-free diet of HLA-DQ2 and TRAFD1 gene expression in peripheral blood of celiac disease patients.Journal of translational autoimmunity · 2024Article
- Coexistence of apoptosis, pyroptosis, and necroptosis pathways in celiac disease.Clinical and experimental immunology · 2023Article
- Sex bias in celiac disease: XWAS and monocyte eQTLs in women identify TMEM187 as a functional candidate gene.Biology of sex differences · 2023Article
- Peroxiredoxins and Hypoxia-Inducible Factor-1α in Duodenal Tissue: Emerging Factors in the Pathophysiology of Pediatric Celiac Disease Patients.Current issues in molecular biology · 2023Article
- Molecular mechanism of miRNA-23a in sepsis-induced lung injury.American journal of translational research · 2023Article
- Interactions between PCSK9 and NLRP3 inflammasome signaling in atherosclerosis.Frontiers in immunology · 2023Review
- Toll-like Receptors and Celiac Disease.International journal of molecular sciences · 2022Review
- The modulation of macrophage subsets in celiac disease pathogenesis.Immunity, inflammation and disease · 2022Review
- Functional implications of the CpG island methylation in the pathogenesis of celiac disease.Molecular biology reports · 2022Review
- Celiac Disease and Targeting the Molecular Mechanisms of Autoimmunity in COVID Pandemic.International journal of molecular sciences · 2022Review
- Baicalin inhibits inflammation of lipopolysaccharide-induced acute lung injury toll like receptor-4/myeloid differentiation primary response 88/nuclear factor-kappa B signaling pathway.Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan · 2022Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Celiac disease (CD) is a gluten-responsive, chronic inflammatory enteropathy. IL-1 cytokine family members IL-1β and IL-18 have been associated with the inflammatory conditions in CD patients. However, the mechanisms of IL-1 molecule activation in CD have not yet been elucidated. We show in this study that peripheral blood mononuclear cells (PBMC) and monocytes from celiac patients responded to pepsin digest of wheat gliadin fraction (PDWGF) by a robust secretion of IL-1β and IL-1α and a slightly elevated production of IL-18. The analysis of the upstream mechanisms underlying PDWGF-induced IL-1β production in celiac PBMC show that PDWGF-induced de novo pro-IL-1β synthesis, followed by a caspase-1 dependent processing and the secretion of mature IL-1β. This was promoted by K+ efflux and oxidative stress, and was independent of P2X7 receptor signaling. The PDWGF-induced IL-1β release was dependent on Nod-like receptor family containing pyrin domain 3 (NLRP3) and apoptosis-associated speck like protein (ASC) as shown by stimulation of bone marrow derived dendritic cells (BMDC) from NLRP3(-/-) and ASC(-/-) knockout mice. Moreover, treatment of human PBMC as well as MyD88(-/-) and Toll-interleukin-1 receptor domain-containing adaptor-inducing interferon-β (TRIF)(-/-) BMDC illustrated that prior to the activation of caspase-1, the PDWGF-triggered signal constitutes the activation of the MyD88/TRIF/MAPK/NF-κB pathway. Moreover, our results indicate that the combined action of TLR2 and TLR4 may be required for optimal induction of IL-1β in response to PDWGF. Thus, innate immune pathways, such as TLR2/4/MyD88/TRIF/MAPK/NF-κB and an NLRP3 inflammasome activation are involved in wheat proteins signaling and may play an important role in the pathogenesis of CD.
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Registered trials
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