Pro-inflammatory properties and neutrophil activation by Helicobacter pylori urease
| Autor: | Adriele Scopel-Guerra, Célia R. Carlini, Augusto F. Uberti, Christina Barja-Fidalgo, Deiber Olivera-Severo, German Enrique Wassermann, João Alfredo Moraes, Pedro Barcellos-de-Souza |
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| Rok vydání: | 2013 |
| Předmět: |
Male
Neutrophils Lipoxygenase Apoptosis Inflammation Toxicology Neutrophil Activation Helicobacter Infections Microbiology Mice medicine Gastric mucosa Animals Humans chemistry.chemical_classification Reactive oxygen species Helicobacter pylori biology Chemotaxis biology.organism_classification Urease Recombinant Proteins Chemotaxis Leukocyte medicine.anatomical_structure chemistry Gastric Mucosa Immunology biology.protein Cyclooxygenase medicine.symptom Reactive Oxygen Species |
| Zdroj: | Toxicon. 69:240-249 |
| ISSN: | 0041-0101 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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