RECOMBINANT HELICOBACTER-PYLORI UREASE ACTIVATES PRIMARY MUCOSAL MACROPHAGES

Helicobacter pylori urease is absorbed into the gastric mucosa at site s of inflammation, but whether the enzyme activates mucosal macrophage s is not known. Because mucosal macrophages differ phenotypically and functionally from blood monocytes, whether recombinant H. pylori ureas e (rUrease) activated purified lamina propria macrophages in vitro was investigated. rUrease (1-10 mu g/mL) induced primary mucosal macropha ges to produce interleukin (IL)-1 beta, IL-6, and tumor necrosis facto r (TNF)-alpha but not IL-8 proteins in a dose-dependent manner (P < .0 5 to P < .001). Quantitative reverse transcriptase-polymerase chain re action using capillary electrophoresis laser-induced fluorescence show ed that rUrease (0.1-10 mu g/mL) also induced dose-dependent expressio n of IL-1 beta, IL-6, and TNF-alpha but not IL-8 mRNA (P < .05), sugge sting that rUrease-induced production of certain cytokines is regulate d at the level of gene transcription. These findings indicate that the ability of H. pylori urease to activate mucosal macrophages, resultin g in production of proinflammatory cytokines, may be involved in the p athogenesis of H. pylori-associated mucosal inflammation.