Effect of interlukin-1beta on proliferation of gastric epithelial cells in culture.
BACKGROUND
Helicobacter pylori is the main risk factor for the development of non-cardia gastric cancer. Increased proliferation of the gastric mucosa is a feature of H. pylori infection. Mucosal interkeukin-1beta production is increased in H. pylori infection and IL-1beta genotypes associated with increased pro-inflammatory activity are risk factors for the development of gastric cancer. The effect of IL-1beta on gastric epithelial cell proliferation has been examined in this study.


METHODS
AGS cells were cultured with IL-1beta. DNA synthesis was assed by [3H]thymidine incorporation and total viable cell numbers by MTT assay.


RESULTS
IL-1beta dose dependently increased DNA synthesis and cell numbers. The enhanced proliferation was blocked by interleukin-1 receptor antagonist. Addition of neutralising antibody to GM-CSF reduced IL-1beta-stimulated proliferation by 31 +/- 4 %. GM-CSF alone significantly stimulated proliferation. Addition or neutralisation of IL-8 had no effect on basal or IL-1beta-stimulated proliferation. The tyrosine kinase inhibitor genistein completely blocked IL-1beta-stimulated proliferation and inhibition of the extracellular signal related kinase pathway with PD 98059 inhibited IL-1beta stimulated proliferation by 58 +/- 5 %.


CONCLUSIONS
IL-1beta stimulates proliferation in gastric epithelial cells. Autocrine stimulation by GM-CSF contributes to this proliferative response. Signalling via tyrosine kinase activity is essential to the mitogenic response to IL-1beta. The extracellular signal related kinase pathway is involved in, but not essential to downstream signalling. IL-1beta may contribute to the hyperproliferation seen in H. pylori- infected gastric mucosa, and be involved in the carcinogenic process.
Beales
Ian L P
IL
Department of Cell Biology School of Medicine, Health Policy and Practice, University of East Anglia Norwich, NR4 7TJ, United Kingdom. ibeales@uea.ac.uk
D002452:Cell Count; D002455:Cell Division / Q000187:drug effects; D002471:Cell Transformation, Neoplastic; D004247:DNA / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects; D005753:Gastric Mucosa / Q000166:cytology / Q000187:drug effects*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D016481:Helicobacter Infections / Q000150:complications; D016480:Helicobacter pylori; D006801:Humans; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000494:pharmacology; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors; D013274:Stomach Neoplasms / Q000382:microbiology / Q000473:pathology; D013936:Thymidine / Q000378:metabolism; D014407:Tumor Cells, Cultured
D007375:Interleukin-1; D017472:Receptors, Interleukin-1; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D004247:DNA; D011505:Protein-Tyrosine Kinases; D020929:Mitogen-Activated Protein Kinase Kinases; D013936:Thymidine