Distinct mechanism of helicobacter pylori-mediated NF-kappa B activation between gastric cancer cells and monocytic cells

NF-kappaB is a critical regulator of genes involved in inflammation. Gastri c epithelial cells and macrophages are considered the main sources of pro-i nflammatory cytokines. We investigated NF-kappaB activation by Helicobacter pylori in MKN45 gastric epithelial cells and THP-1 monocytic cells. Althou gh, cag pathogenicity island (PAI)-positive H. pylori (wild type) activated NF-kappaB in both cells, isogenic mutant of cagE (Delta cagE) activated it only in THP-1 cells. Supernatant from the wild type culture could activate NF-kappaB in THP-1 cells but not in MKN45 cells. High density cDNA array a nalysis revealed that mRNA expression of NF-kappaB-regulated genes such as interleukin (IL)-8, tumor necrosis factor-alpha (TNF alpha), and IL-1 beta was significantly up-regulated by the wild type in both cells, whereas it w as up-regulated by Delta cagE only in THP-1 cells. Experiments using CD14-n eutralizing antibody and IL-1 receptor-associated kinase (IRAK) assay showe d that both wild type and Delta cagE H. pylori activated NF-kappaB through CD14 and IRAK in THP-1 cells but not in MKN45 cells. Macrophages from C3H/H eJ mice carrying point mutation in the Toll-like receptor 4 (TLR4) gene sho wed decreased NF-kappaB activation and TNFa secretion compared with C3H/HeN mouse macrophage when treated with H. pylori. In conclusion, H. pylori-ind uced NF-kappaB activation in epithelial cells is dependent on cag PAI and c ontact but does not involve CD14 and IRAK, whereas in macrophage/monocytic cells it is independent of cag PAI or contact but involves CD14 and TLR4.