HELICOBACTER-PYLORI STIMULATES GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR (GM-CSF) PRODUCTION FROM CULTURED ANTRAL BIOPSIES AND A HUMAN GASTRIC EPITHELIAL-CELL LINE

Objective: To examine the regulation of granulocyte-macrophage colony- stimulating factor (GM-CSF) production by gastric epithelial cells in Helicobacter pylori infection. Design: The effect of H. pylori infecti on 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 G M-CSF was assessed by enzyme-linked immunosorbent assay. The mechanism of stimulation of GM-CSF production was examined by coculture 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 acti ve phorbol ester, phorbol myristate acetate (PMA), significant release of GM-CSF was seen. H. pylori-positive biopsies produced significantl y more GM-CSF in both the unstimulated and PMA-stimulated state than H . pylori-negative biopsies. Constitutive release of GM-CSF from cultur ed human gastric AGS cells could be significantly enhanced by co-cultu re with live H. pylori or the addition of interteukin-1 beta, tumour n ecrosis factor alpha and PMA, but not by exposure to forskolin. The pr otein kinase C inhibitor staurosporine abolished the stimulatory effec t of PMA on ACS cells, whereas the protein-tyrosine kinase inhibitor h erbimycin A prevented the stimulation of GM-CSF production seen with H . pylori and both cytokines. Conclusion: H. pylori enhances GM-CSF pro duction by gastric epithelia. H. pylori appears to stimulate gastric e pithelial cells directly to produce GM-CSF and this stimulation involv es a tyrosine kinase dependent step. Induction of GM-CSF may play a ro le in the initiation and perpetuation of gastric inflammation in H. py lori infection.