1. Pathways involved in regulation of macrophage iNOS synthesis and NO production in response to H. pylori.
Pathways involved in regulation of macrophage iNOS synthesis and NO production in response to H. pylori. The translation of iNOS protein depends on the availability of l-arginine (l-Arg). Pathogenic mechanisms that inhibit l-Arg availability for iNOS include (i) the consumption of extracellular l-Arg by H. pylori itself, through its bacterial arginase activity; (ii) the upregulation of macrophage arginase II, which depletes intracellular l-Arg; and (iii) induction of ODC that generates the polyamine spermine, which blocks uptake of l-Arg into macrophages by CAT2. The resulting effect is limitation of iNOS protein synthesis and NO production, despite high levels of iNOS mRNA. Arginase and ODC are novel targets for therapeutic intervention to enhance antimicrobial NO production and hence reduce persistent colonization that leads to chronic inflammation and cancer risk.
Lydia E. Wroblewski et al. Clin. Microbiol. Rev. 2010; doi: /CMR