title: IL-11 is a parietal cell cytokine that induces atrophic gastritis.
abstract: OBJECTIVE
  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.
authors.affiliation: Murdoch Children's Research Institute, Royal Children's Hospital, Flemington Road, Parkville, VIC 3052, Australia.
authors.forename: Meegan
authors.initials: M
authors.lastname: Howlett
authors.forename: Heather V
authors.initials: HV
authors.lastname: Chalinor
authors.forename: Jon N
authors.initials: JN
authors.lastname: Buzzelli
authors.forename: Nhung
authors.initials: N
authors.lastname: Nguyen
authors.forename: Ian R
authors.initials: IR
authors.lastname: van Driel
authors.forename: Katrina M
authors.initials: KM
authors.lastname: Bell
authors.forename: James G
authors.initials: JG
authors.lastname: Fox
authors.forename: Eva
authors.initials: E
authors.lastname: Dimitriadis
authors.forename: Trevelyan R
authors.initials: TR
authors.lastname: Menheniott
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Giraud
authors.forename: Louise M
authors.initials: LM
authors.lastname: Judd
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D005744:Gastric Acid / Q000378:metabolism; D005757:Gastritis, Atrophic / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D016481:Helicobacter Infections / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D016480:Helicobacter pylori; D006801:Humans; D015151:Immunoblotting; D017370:Interleukin-11 / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis; D010295:Parietal Cells, Gastric / Q000378:metabolism* / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000378:metabolism
chemical_list: D015415:Biomarkers; D017370:Interleukin-11; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse