INDUCTION OF HOST SIGNAL-TRANSDUCTION PATHWAYS BY HELICOBACTER-PYLORI

Adherence of Helicobacter pylori to cultured gastric epithelial cells is associated with several cellular events, including the tyrosine pho sphorylation of a 145-kDa host protein; the reorganization of the host cell actin and associated cellular proteins, like vasodilator-stimula ted phosphoprotein, adjacent to the attached bacterial cell; and the s ubsequent release of the cytokine, interleukin 8 (IL-8). H. pylori iso lated from patients with ulcer disease and gastric cancer contain a DN A insertion, the cag pathogenicity island (PAI), that is not present i n bacteria isolated from individuals with asymptomatic infection. Muta tions in a number of PAI genes abolish tyrosine phosphorylation and IL -8 synthesis but not the cytoskeletal rearrangements. Kinase inhibitio n studies suggest there are two distinct pathways operative in stimula ting IL-8 release from host cells and one of these H. pylori pathways is independent of the tyrosine phosphorylation step.