title: Helicobacter pylori stimulates granulocyte-macrophage colony-stimulating factor (GM-CSF) production from cultured antral biopsies and a human gastric epithelial cell line.
abstract: OBJECTIVE
  To examine the regulation of granulocyte-macrophage colony-stimulating factor (GM-CSF) production by gastric epithelial cells in Helicobacter pylori infection.
  
  
  METHODS
  The effect of H. pylori infection on gastric GM-CSF production was assessed using short-term culture of antral biopsies. The mechanism of GM-CSF induction was investigated using a gastric epithelial cancer cell line.
  
  
  METHODS
  Production of GM-CSF was assessed by enzyme-linked immunosorbent assay. The mechanism of stimulation of GM-CSF production was examined by co-culture of AGS carcinoma cells with H. pylori and specific stimulants and inhibitors.
  
  
  RESULTS
  Biopsies from H. pylori-negative patients in the basal state did not produce GM-CSF. However, over 24 h in the presence of the active phorbol ester, phorbol myristate acetate (PMA), significant release of GM-CSF was seen. H. pylori-positive biopsies produced significantly more GM-CSF in both the unstimulated and PMA-stimulated state than H. pylori-negative biopsies. Constitutive release of GM-CSF from cultured human gastric AGS cells could be significantly enhanced by co-culture with live H. pylori or the addition of interleukin-1 beta, tumour necrosis factor alpha and PMA, but not by exposure to forskolin. The protein kinase C inhibitor staurosporine abolished the stimulatory effect of PMA on AGS cells, whereas the protein-tyrosine kinase inhibitor herbimycin A prevented the stimulation of GM-CSF production seen with H. pylori and both cytokines.
  
  
  CONCLUSIONS
  H. pylori enhances GM-CSF production by gastric epithelia. H. pylori appears to stimulate gastric epithelial cells directly to produce GM-CSF and this stimulation involves a tyrosine kinase dependent step. Induction of GM-CSF may play a role in the initiation and perpetuation of gastric inflammation in H. pylori infection.
authors.affiliation: Department of Gastroenterology, Royal Postgraduate Medical School, Hammersmith Hospital, London, UK.
authors.forename: I L
authors.initials: IL
authors.lastname: Beales
authors.forename: J
authors.initials: J
authors.lastname: Calam
mesh_terms: D000230:Adenocarcinoma / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D001431:Bacteriological Techniques; D001706:Biopsy; D002273:Carcinogens / Q000494:pharmacology; D002908:Chronic Disease; D004797:Enzyme-Linked Immunosorbent Assay; D004848:Epithelium / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D005753:Gastric Mucosa / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D005773:Gastroscopy; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis* / Q000187:drug effects; D016481:Helicobacter Infections / Q000150:complications / Q000378:metabolism; D016480:Helicobacter pylori / Q000302:isolation & purification / Q000502:physiology*; D006801:Humans; D011706:Pyloric Antrum / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D013274:Stomach Neoplasms / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: D002273:Carcinogens; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D013755:Tetradecanoylphorbol Acetate