More and more evidences are pointing to an important role of the

More and more evidences are pointing to an important role of the arachidonic acid pathway in the development of chronic inflammation and gastric carcinogenesis (Wang and Dubois, 2010; Wymann and Schneiter, 2008). Lipoxygenase metabolites such as LTB4 enhance the proliferation of epithelial cells and may induce oncogenes in these cells (Wang and Dubois, 2010). Our data show that nanomolar doses of HPU directly activates human neutrophils. Chemotaxis induced by 100 nM rHPU was similar to that produced by 100 nM fMLP, a synthetic peptide that mimicks bacterial peptides (Niedel et al., 1979). The chemotactic effect of rHPU did not require its enzymatic activity.

Additionally, histology sections of rHPU-induced edema showed an increased neutrophil infiltration. We have previously reported that the plant urease canatoxin induced neutrophil migration into rat pleural cavity and “air-pouches” and also Pexidartinib that macrophages exposed

to canatoxin released a neutrophil-chemotactic factor (Barja-Fidalgo et al., 1992). Other studies have shown that purified H. pylori urease directly activated primary human blood monocytes and stimulated dose-dependent production of inflammatory cytokines ( Harris et al., 1996). The neutrophil activating protein HP-NAP is a dodecameric protein, structurally similar to bacterioferritines, which activates neutrophils by stimulating the production www.selleckchem.com/products/forskolin.html of reactive forms of oxygen (D’Elios et al., 2007; Evans et al., 1995; Zanotti et al., 2002). In monocytes HP-NAP induces activation and synthesis of cytokines, plasminogen activator inhibitor-2 and tissue factor (Montemurro et al., 2001). HP-NAP was shown to increase the lifespan of neutrophils and monocytes indirectly through the release of endogenous pro-survival factors (Cappon et al., 2010). Preliminary data suggest that rHPU is as powerful as HP-NAP in promoting activation of monocytes with induction of mRNA synthesis for the cytokines IL1b, IL6,

IL8, IL23 and TNFα (Olivera-Severo, D and De Bernard M, unpublished data). As proposed for HP-NAP (De Bernard Florfenicol and D’Elios, 2010), HPU is released most likely after lysis of H. pylori cells, reaching the underlying tissue and lamina propria where it would exert its pro-inflammatory effects, synergistically with other bacterial factors, recruiting neutrophils and monocytes, and activating platelets within nearby injured microcapillaries. Enarsson et al., 2005, reported that H. pylori promoted significant T-cell activation and transendothelial migration in a model of human umbilical vein endothelial cells and that purified H. pylori urease induced a migratory effect similar to that of whole bacteria. Mutant H. pylori negative for the urease A subunit still promoted significant T-cell migration, an effect that was imparted as a contribution of the functional cag pathogenicity island ( Enarsson et al., 2005).

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