ArticlePloS one2012
Helicobacter pylori CagA triggers expression of the bactericidal lectin REG3γ via gastric STAT3 activation.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 67 citations in OpenAlex.
- Diet-Induced Obesity ExacerbatesbioRxiv : the preprint server for biology · 2026Article
- Upregulation of innate and adaptive immune mechanisms facilitating prevention of gastricFrontiers in immunology · 2026Article
- REG3A: A Multifunctional Antioxidant Lectin at the Crossroads of Microbiota Regulation, Inflammation, and Cancer.Cancers · 2025Review
- A single amino acid in the Salmonella effector SarA/SteE triggers supraphysiological activation of STAT3 for anti-inflammatory gene expression.Cell reports · 2025Article
- GRB7-mediated enhancement of cell malignant characteristics induced byFrontiers in microbiology · 2024Article
- Reduction of UreB and CagA expression level by siRNA construct in Helicobacter pylori strain SS1.BMC microbiology · 2023Article
- A review of signal pathway induced by virulent protein CagA ofFrontiers in cellular and infection microbiology · 2023Review
- Curcumin's prevention of inflammation-driven early gastric cancer and its molecular mechanism.Chinese herbal medicines · 2022Review
- Peripheral Cytokine Levels as a Prognostic Indicator in Gastric Cancer: A Review of Existing Literature.Biomedicines · 2021Review
- Transcriptional programmes underlying cellular identity and microbial responsiveness in the intestinal epithelium.Nature reviews. Gastroenterology & hepatology · 2021Review
- Dietary intake of walnut preventedJournal of clinical biochemistry and nutrition · 2021Article
- Walnut polyphenol extracts inhibitJournal of clinical biochemistry and nutrition · 2020Article
- Structure of cytotoxic associated antigen A protein ofVeterinary world · 2020Article
- Controversial Roles of Gut Microbiota-Derived Short-Chain Fatty Acids (SCFAs) on Pancreatic β-Cell Growth and Insulin Secretion.International journal of molecular sciences · 2020Review
- Increased LIGHT expression and activation of non-canonical NF-κB are observed in gastric lesions of MyD88-deficient mice upon Helicobacter felis infection.Scientific reports · 2019Article
- Decreased IL-17RB expression impairs CD11bCell death & disease · 2019Article
- Interleukin-33 Promotes REG3γ Expression in Intestinal Epithelial Cells and Regulates Gut Microbiota.Cellular and molecular gastroenterology and hepatology · 2019Article
- Salmonella Activation of STAT3 Signaling by SarA Effector Promotes Intracellular Replication and Production of IL-10.Cell reports · 2018Article
- Activation of Signal Transduction and Activator of Transcription 3 Signaling Contributes toGastroenterology research and practice · 2018Article
- Significance of Interleukin-6/STAT Pathway for the Gene Expression of REG Iα, a New Autoantigen in Sjögren's Syndrome Patients, in Salivary Duct Epithelial Cells.Clinical reviews in allergy & immunology · 2017Review
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMost of what is known about the Helicobacter pylori (H. pylori) cytotoxin, CagA, pertains to a much-vaunted role as a determinant of gastric inflammation and cancer. Little attention has been devoted to potential roles of CagA in the majority of H. pylori infected individuals not showing oncogenic progression, particularly in relation to host tolerance. Regenerating islet-derived (REG)3γ encodes a secreted C-type lectin that exerts direct bactericidal activity against Gram-positive bacteria in the intestine. Here, we extend this paradigm of lectin-mediated innate immunity, showing that REG3γ expression is triggered by CagA in the H. pylori-infected stomach. METHODOLOGY/PRINCIPAL
findingsIn human gastric mucosal tissues, REG3γ expression was significantly increased in CagA-positive, compared to CagA-negative H. pylori infected individuals. Using transfected CagA-inducible gastric MKN28 cells, we recapitulated REG3γ induction in vitro, also showing that tyrosine phosphorylated, not unphosphorylated CagA triggers REG3γ transcription. In concert with induced REG3γ, pro-inflammatory signalling downstream of the gp130 cytokine co-receptor via the signal transducer and activator of transcription (STAT)3 and transcription of two cognate ligands, interleukin(IL)-11 and IL-6, were significantly increased. Exogenous IL-11, but not IL-6, directly stimulated STAT3 activation and REG3γ transcription. STAT3 siRNA knockdown or IL-11 receptor blockade respectively abrogated or subdued CagA-dependent REG3γ mRNA induction, thus demonstrating a requirement for uncompromised signalling via the IL-11/STAT3 pathway. Inhibition of the gp130-related SHP2-(Ras)-ERK pathway did not affect CagA-dependent REG3γ induction, but strengthened STAT3 activation as well as augmenting transcription of mucosal innate immune regulators, IL-6, IL-8 and interferon-response factor (IRF)1. CONCLUSIONS/SIGNIFICANCE: Our results support a model of CagA-directed REG3γ expression in gastric epithelial cells via activation of the IL-11/gp130/STAT3 pathway. This response might allow Gram-negative H. pylori to manipulate host immunity to favour its own survival, by reducing the fitness of co-habiting Gram-positive bacteria with which it competes for resources in the gastric mucosal niche.
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