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IL-11 is a parietal cell cytokine that induces atrophic gastritis.

ABSTRACT: IL-is important in gastric damage, mucosal repair and gastric cancer progression. We analysed IL-11 expression in H.pylori infected mouse stomach, the site of gastric IL-11 expression in mice and humans, and the effect of exogenous IL-11 on gastric mucosal homeostasis.IL-11 protein was localised in mouse and human stomach. The impact of chronic, exogenous IL-11 on normal mouse stomach was examined histologically and transcriptionally by microarray, confirmed by mRNA and protein analysis. Functional impact of IL-11 on gastric acid secretion was determined.In mice infected with H.pylori, IL-11 was increased in fundic mucosa with temporal expression similar to IL-1b. IL-11 protein was localised predominantly to parietal cells in mouse and human stomach. Application of exogenous IL-11 to resulted in fundic parietal and chief cell loss, hyperplasia, mucous cell metaplasia and inflammation. Coincident with cellular changes were an increased gastric pH, altered parietal cell ultrastructure and altered gene expression, particularly genes involved in immune response and ion transport which could result in compromised acid secretion. We confirmed that a single dose of IL-11 effectively ablated the gastric response to histamine.IL-11 is a parietal cell cytokine that blocks gastric acid secretion, likely via reducing expression of parietal cell ion transport genes, CCKb and histamine H2 receptors. IL-11 expression is increased in H. pylori infected mouse stomach and treatment of wild type mice with IL-11 induced changes in the gastric fundic mucosa reminiscent of chronic atrophic gastritis, a precursor to gastric cancer.

SUBMITTER: Howlett M

PROVIDER: S-EPMC3471558 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature

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IL-11 is a parietal cell cytokine that induces atrophic gastritis.

Howlett Meegan M Chalinor Heather V HV Buzzelli Jon N JN Nguyen Nhung N van Driel Ian R IR Bell Katrina M KM Fox James G JG Dimitriadis Eva E Menheniott Trevelyan R TR Giraud Andrew S AS Judd Louise M LM

Gut 20111216 10

<h4>Background and aims</h4>IL-is important in gastric damage, mucosal repair and gastric cancer progression. We analysed IL-11 expression in H.pylori infected mouse stomach, the site of gastric IL-11 expression in mice and humans, and the effect of exogenous IL-11 on gastric mucosal homeostasis.<h4>Methods</h4>IL-11 protein was localised in mouse and human stomach. The impact of chronic, exogenous IL-11 on normal mouse stomach was examined histologically and transcriptionally by microarray, con ...[more]

PMID: 22180059

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Project description:BackgroundAtrophic gastritis (AG), which is characterized by a decreased number or disappearance of the glandular structures and secretory dysfunction, is linked to chronically inflamed stomach. It has been estimated that the annual incidence of gastric cancer (GC) is 0.1% for patients with AG. Early eradication of Helicobacter pylori (H. pylori) can reduce the risk of GC development. Additionally, the follow-up and management of AG are necessary to prevent GC. Exploring novel methods of the automatized analysis of data for apprehending knowledge in any medical field is encouraged, especially when a body of literature suggests the necessity of doing so. Accordingly, herein, we aim to systematically review the current foci and status of AG research using bibliometric analysis.MethodsArticles and reviews related to AG published from 2011 to 2021 in the Web of Science Core Collection were retrieved. Microsoft Office Excel 2019 and GraphPad Prism were used to show the annual number of publications and scientific productivity of authors through time. CiteSpace and VOSviewer were used to generate network maps about the collaborations among countries, institutions, and authors as well as reveal hotspots of AG research. The relationships among the author's keywords, cited references, and the top authors were summarized by a Sankey plot (three-fields plot).ResultsA total of 1,432 publications were included in the present study. China remained the most productive country, with the highest number of publications (377, 26.32%). Vanderbilt University contributed the most publications of any single institution (56, 3.91%). James R Goldenring was the most active and influential scholar, with the highest number of publications and greatest centrality. The most prolific journal in this field was World Journal of Gastroenterology (62, 4.32%). Gastroenterology (997, 69.62%) was the most co-cited journal. Exploring the origin of gastric metaplasia, especially spasmolytic polypeptide-expressing metaplasia (SPEM) was a major topic in AG research.ConclusionsThis bibliometric study provides a comprehensive analysis of the scientific progress of AG over the past decade. Metaplasia is a hot topic and could be a promising area of research in the coming years.

Project description:Despite a global decrease, gastric cancer (GC) incidence appears to be increasing recently in young, particularly female, patients. The causal mechanism for this "new" type of GC is unknown, but a role for autoimmunity is suggested. A cascade of gastric precancerous lesions, beginning with chronic atrophic gastritis (CAG), precedes GC. To test the possible existence of autoimmunity in patients with CAG, we aimed to analyze the prevalence of several autoantibodies in patients with CAG as compared to control patients. Sera of 355 patients included in our previous prospective, multicenter study were tested for 19 autoantibodies (anti-nuclear antibodies, ANA, anti-parietal cell antibody, APCA, anti-intrinsic factor antibody, AIFA, and 16 myositis-associated antibodies). The results were compared between CAG patients (n = 154), including autoimmune gastritis patients (AIG, n = 45), non-autoimmune gastritis patients (NAIG, n = 109), and control patients (n = 201). ANA positivity was significantly higher in AIG than in NAIG or control patients (46.7%, 29%, and 27%, respectively, p = 0.04). Female gender was positively associated with ANA positivity (OR 0.51 (0.31-0.81), p = 0.005), while age and H. pylori infection status were not. Myositis-associated antibodies were found in 8.9% of AIG, 5.5% of NAIG, and 4.4% of control patients, without significant differences among the groups (p = 0.8). Higher APCA and AIFA positivity was confirmed in AIG, and was not associated with H. pylori infection, age, or gender in the multivariate analysis. ANA antibodies are significantly more prevalent in AIG than in control patients, but the clinical significance of this finding remains to be established. H. pylori infection does not affect autoantibody seropositivity (ANA, APCA, AIFA). The positivity of myositis-associated antibodies is not increased in patients with CAG as compared to control patients. Overall, our results do not support an overrepresentation of common autoantibodies in patients with CAG.

Dataset Information

IL-11 is a parietal cell cytokine that induces atrophic gastritis.

Publications

IL-11 is a parietal cell cytokine that induces atrophic gastritis.

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