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IL-11 is a parietal cell cytokine that induces atrophic gastritis
  1. Meegan Howlett1,
  2. Heather V Chalinor1,
  3. Jon N Buzzelli1,
  4. Nhung Nguyen2,
  5. Ian R van Driel2,
  6. Katrina M Bell1,
  7. James G Fox3,
  8. Eva Dimitriadis4,
  9. Trevelyan R Menheniott1,
  10. Andrew S Giraud1,5,
  11. Louise M Judd1,5
  1. 1Murdoch Children's Research Institute, Royal Children's Hospital, Parkville, Victoria, Australia
  2. 2Department of Biochemistry and Molecular Biology, Bio 21 Molecular Sciences and Biotechnology Institute, University of Melbourne, Parkville, Victoria, Australia
  3. 3MIT, Department of Comparative Medicine, Boston, Massachusetts, USA
  4. 4Prince Henrys Institute, Monash University, Clayton, Victoria, Australia
  5. 5Department of Paediatrics, University of Melbourne, Royal Children's Hospital, Flemington Road, Parkville, Victoria, Australia
  1. Correspondence to Dr Louise M Judd, Murdoch Children's Research Institute, Royal Children's Hospital, Flemington Road, Parkville, VIC 3052, Australia; louise.judd{at}mcri.edu.au

Abstract

Background and Aims 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.

Methods 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.

Results 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.

Conclusions 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.

  • Acid secretion
  • atrophy
  • cancer
  • carcinogenesis
  • chronic atrophic gastritis
  • cytokines
  • epithelial cells
  • epithelial differentiation
  • gastric adenocarcinoma
  • gastric cancer
  • gastric carcinoma
  • gastric metaplasia
  • gastric wound repair
  • gastrin releasing peptides
  • gastrointestinal neoplasia
  • Helicobacter pylori—pathogenesis
  • IL-11
  • inflammation
  • molecular carcinogenesis
  • mucosal barrier
  • trefoil factors
  • trefoil peptides

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Footnotes

  • Funding This study was supported by the Victorian Government's Operational Infrastructure Support Program and NH&MRC Australia #APP1008776.

  • Competing interests None.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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