Figure 4 The H. pylori rocF- mutant induces more IL-8 and MIP-1 β in AGS cells than wild type H. pylori, as determined by Bioplex. Supernatants from H. pylori infected-AGS cells were collected and used to determine the concentration Liproxstatin-1 purchase of IL-8 and MIP-1β (pg/ml) A. Levels of IL-8; one-way ANOVA p < 0.0001; *p = 0.0001 (rocF- vs NS); #p = 0.0249 (rocF- vs WT); **p = 0.044 (rocF- vs rocF +); B. Levels of MIP-1B; one-way ANOVA p < 0.0001; *p < 0.0001 (rocF- vs NS); #p < 0.0001 (rocF- vs WT); p = 0.0001 (rocF- vs rocF + ). Values in both Figures represent the average signal ± SEM

of four independent replicates. Figure 5 The rocF mutant of H. pylori induces more IL-8 in AGS cells compared with wild type H. pylori, as determined

by ELISA analysis. Please see legend on Figure 4 for IL-8. One-way ANOVA p = 0.0002; selleck products *p = 0.0003 (rocF- vs NS); #p = 0.045 (rocF- vs WT); **p = 0.0185 (rocF- vs rocF +). Values represent the average signal ± SEM of four independent replicates. Discussion While it is well-known that H. pylori induces inflammation, this inflammatory response is insufficient to clear the organism from the gastric mucosa and the organism overcomes the immune response to cause chronic infections that can last for decades in untreated patients. Paradoxically, H. pylori may have both pro-inflammatory as well as anti-inflammatory mechanisms. These opposing forces must operate in such a fashion as to achieve a delicate balance that involves complex interactions between bacterial virulence factors and host innate and adaptive immune system factors. How does arginase in wild type H. pylori act as an anti-inflammatory mediator? While the underlying mechanisms are still not well understood, the depletion of arginine by this enzyme from the extracellular environment may be one factor that triggers altered gene expression in the gastric epithelial cell. Precedence for this idea comes from prior work showing that

arginine depletion leads to altered T cell Thiamet G ABT-263 solubility dmso receptor zeta chain expression (CD3ζ) [16]. Another possibility is that the products of arginine hydrolysis, namely, ornithine and urea, could also be playing a role in altering transcriptional responses by the gastric epithelial cells. A third possibility is that the arginase mutant, through disruption of the bacterial metabolic balance of arginine, ornithine, or urea levels, could have altered gene transcriptional profiles leading to modified expression of other bacterial virulence factors that interplay with the host immune system. A fourth possibility is that the increase in IL-8 production induced by the H. pylori rocF- mutant is through altered spermine produced by the AGS cells. Previous reports have shown that H. pylori infection induces ornithine decarboxylase (ODC) in macrophages [15, 18]. ODC degrades L-ornithine into putrescine and this is later converted into spermidine and finally spermine.