Handa et al., 2010, reported that H. pylori infection stimulates inflammatory cells within the gastric tissue to release ROS ( Handa et al., 2010) which correlates with higher levels of DNA repair in gastric epithelial cells ( Machado et al., 2010). Studies by Allen et al. (2005), showed that H. pylori infection interferes on the activity of human neutrophil NADPH oxidase leading to extracellular release of ROS ( Allen, 2001). Here, we demonstrated that rHPU-activated neutrophils release ROS extracellularly potentially contributing
to damage the gastric tissue. The half-life of human neutrophils is typically of 12 h, as a result of the constitutive expression of pro-apoptosis selleck chemicals llc proteins and almost non-detectable levels of anti-apoptosis proteins (Witko-Sarsat et al., 2011). Neutrophils release proteolytic enzymes and ROS that inflict local tissue damage and are removed from the inflammatory site by induction of apoptosis. Thus fine regulation of pro- and anti-apoptosis proteins that control neutrophil
lifespan is a critical process for the resolution of inflammation. Our data show that rHPU delays neutrophils apoptosis, prolonging their survival and contributing to the underlying local tissue inflammation, as seen in the mouse paw edema assay. Increased lifespan of rHPU-activated neutrophils was accompanied by reduced levels of the pro-apoptotic protein Bad and induction of expression of the anti-apoptotic protein Bcl-XL, a situation that would ultimately lead to a persistent inflammatory status. In agreement with our data, other groups have demonstrated that products from click here of H. pylori exert an important role in maintaining inflammation, by suppressing human neutrophil apoptosis ( Cappon et al., 2010; Kim et al., 2001). Interestingly, other studies demonstrated that H. pylori can induce apoptosis in gastric epithelial cell lines ( Ashktorab et al., 2008), contributing to the worsening of the gastroduodenal illness. Lipoxygenase products contribute to the
anti-apoptotic property as well as to chemotaxis induced by HPU as indicated by the AA861 pretreatment of neutrophils. HPU-treated neutrophils had increased levels of lipoxygenases(s) but no alteration of cyclooxygenase(s) content. Our data show that lipoxygenases play an important role in mediating the cell-activating property of HPU (Table 1). Altogether our data demonstrate that HPU, besides its well known role in allowing bacterial gastric colonization, also displays potent pro-inflammatory activity modulated by lipoxygenase-derived eicosanoids. The increased lifespan of HPU-activated neutrophils and its ability to attract more neutrophils toward the injured tissues, acting together with other bacterial factors, potentially amplify the gastric inflammatory process. These findings could be particularly relevant to the mechanisms leading to gastrointestinal disease caused by H.