Cutting edge: urease release by Helicobacter pylori stimulates macrophage inducible nitric oxide synthase.

Gobert AP, Mersey BD, Cheng Y, Blumberg DR, Newton JC, Wilson KT
J Immunol. 2002 168 (12): 6002-6

PMID: 12055207 · DOI:10.4049/jimmunol.168.12.6002

Inducible NO synthase (iNOS) expression and production of NO are both up-regulated with Helicobacter pylori infection in vivo and in vitro. We determined whether major pathogenicity proteins released by H. pylori activate iNOS by coculturing macrophages with wild-type or mutant strains deficient in VacA, CagA, picB product, or urease (ureA(-)). When filters were used to separate H. pylori from macrophages, there was a selective and significant decrease in stimulated iNOS mRNA, protein, and NO(2)(-) production with the ureA(-) strain compared with wild-type and other mutants. Similarly, macrophage NO(2)(-) generation was increased by H. pylori protein water extracts of all strains except ureA(-). Recombinant urease stimulated significant increases in macrophage iNOS expression and NO(2)(-) production. Taken together, these findings indicate a new role for the essential H. pylori survival factor, urease, implicating it in NO-dependent mucosal damage and carcinogenesis.

MeSH Terms (18)

Animals Antigens, Bacterial Cell Line Cells, Cultured Colony Count, Microbial Enzyme Induction Helicobacter pylori Macrophages Mice Mice, Inbred C57BL Mutation Nitric Oxide Nitric Oxide Synthase Nitric Oxide Synthase Type II Nitrites Recombinant Proteins RNA, Messenger Urease

Connections (1)

This publication is referenced by other Labnodes entities: