Cutting edge: urease release by Helicobacter pylori stimulates macrophage inducible nitric oxide synthase.
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.
Gobert
Alain P
AP
Department of Medicine, Division of Gastroenterology, and Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Mersey
Benjamin D
BD
Cheng
Yulan
Y
Blumberg
Darren R
DR
Newton
Jamie C
JC
Wilson
Keith T
KT
D000818:Animals; D000942:Antigens, Bacterial / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002460:Cell Line; D002478:Cells, Cultured; D015169:Colony Count, Microbial; D004790:Enzyme Induction / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D016480:Helicobacter pylori / Q000201:enzymology* / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology; D008264:Macrophages / Q000201:enzymology* / Q000378:metabolism / Q000382:microbiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D009569:Nitric Oxide / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000096:biosynthesis / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D009573:Nitrites / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000494:pharmacology; D014510:Urease / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
D000942:Antigens, Bacterial; D009573:Nitrites; D012333:RNA, Messenger; D011994:Recombinant Proteins; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D014510:Urease