title: Pro-inflammatory properties and neutrophil activation by Helicobacter pylori urease.
abstract: The gastric pathogen Helicobacter pylori produces large amounts of urease, whose enzyme activity enables the bacterium to survive in the stomach. We have previously shown that ureases display enzyme-independent effects in mammalian models, most through lipoxygenases-mediated pathways. Here, we evaluated potential pro-inflammatory properties of H. pylori urease (HPU). Mouse paw edema and activation of human neutrophils were tested using a purified, cell-free, recombinant HPU. rHPU induced paw edema with intense neutrophil infiltration. In vitro 100 nM rHPU was chemotactic to human neutrophils, inducing production of reactive oxygen species. rHPU-activated neutrophils showed increased lifespan, with inhibition of apoptosis accompanied by alterations of Bcl-XL and Bad contents. These effects of rHPU persisted in the absence of enzyme activity. rHPU-induced paw edema, neutrophil chemotaxis and apoptosis inhibition reverted in the presence of the lipoxygenase inhibitors esculetin or AA861. Neutrophils exposed to rHPU showed increased content of lipoxygenase(s) and no alteration of cyclooxygenase(s). Altogether, our data indicate that HPU, besides allowing the bacterial survival in the stomach, could play an important role in the pathogenesis of the gastrointestinal inflammatory disease caused by H. pylori.
authors: Graduate Program in Cellular and Molecular Biology, Center of Biotechnology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
authors: Augusto F
authors: AF
authors: Uberti
authors: Deiber
authors: D
authors: Olivera-Severo
authors: German E
authors: GE
authors: Wassermann
authors: Adriele
authors: A
authors: Scopel-Guerra
authors: João A
authors: JA
authors: Moraes
authors: Pedro
authors: P
authors: Barcellos-de-Souza
authors: Christina
authors: C
authors: Barja-Fidalgo
authors: Célia R
authors: CR
authors: Carlini
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D005753:Gastric Mucosa / Q000187:drug effects / Q000382:microbiology; D016481:Helicobacter Infections / Q000378:metabolism; D016480:Helicobacter pylori / Q000201:enzymology*; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D008084:Lipoxygenase / Q000378:metabolism; D008297:Male; D051379:Mice; D018375:Neutrophil Activation / Q000187:drug effects* / Q000502:physiology; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D014510:Urease / Q000378:metabolism*
chemical_list: D017382:Reactive Oxygen Species; D011994:Recombinant Proteins; D008084:Lipoxygenase; D014510:Urease