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Identified virulence factors of Helicobacter: Proinflammatory effect


HP-NAP (neutrophil activating protein)  

Related genes: napA;
Keywords: Proinflammatory effect;
Structure features:
150-kDa protein oligomer composed of identical 15-kDa subunits antigen.
PDB code: 1JI4.
Figures:
Scheme of the intracellular events involved in HP-Nap activation of human leukocytes (Reproduced from: Montecucco et al., 2001. Helicobacter pylori VacA Vacuolating Cytotoxin and HP-Nap Neutrophil Activating Protein. In Achtman M, Suerbaum S (ed.), Helicobacter pylor: Molecular and Cellular Biology. Norfolk Horizon Scientific Press. Wymondham. pp. 245-262.)


Functions:
H.pylori Neutrophil activating protein, promoting the adhesion of human neutrophils to endothelial cells and the production of reactive oxygen radicals.
Inducing a very moderate state of inflammation that would promote H. pylori growth by the release of nutrient factors from the inflamed tissue.
Mechanism:
Binds to specific receptor which is coupled to a pertussis toxin-sensitive G protein, triggers the entry of calcium through plasma-membrane channels and through the activation of channels located on ER, which are opened by inositol-1,4,5-trisphosphate Ins(1,4,5)P3,produced by activated phospholipase C(PLC). The activated HP-NAP receptor also stimulates a phosphatidylinositol 3-kinase (PI3K) activity. The rise in the cytosolic Ca2+ concentration and the activity of PI3K leads to the activation of renaturable kinases that phosphorylated the cytosolic subunits of the NADPH oxidase of phagocytes, causing their migration to the plasma membrane. Together with the Rac-1 and Rac-2 GTPases, they activate the oxidase activity with production of superoxide anions and reactive oxygen intermediates (RIOs).
References:
Montecucco et al., 2001. Helicobacter pylori VacA Vacuolating Cytotoxin and HP-Nap Neutrophil Activating Protein. In Achtman M, Suerbaum S (ed.), Helicobacter pylor: Molecular and Cellular Biology. Norfolk Horizon Scientific Press. Wymondham. pp. 245-262.
Evans DJ Jr, et al., 1995. Characterization of a Helicobacter pylori neutrophil-activating protein. Infect. Immun. 63(6):2213-2220.
Teneberg S, et al., 1997. Carbohydrate binding specificity of the neutrophil-activating protein of Helicobacter pylori. J. Biol. Chem. 272(30):19067-19071.
Satin B, et al., 2000. The neutrophil-activating protein (HP-NAP) of Helicobacter pylori is a protective antigen and a major virulence factor. J. Exp. Med. 191(9):1467-1476.
Dundon WG, et al., 2002. The neutrophil-activating protein of Helicobacter pylori. Int. J. Med. Microbiol. 291:545-550.
Zanotti G, et al., 2002. Structure of the neutrophil-activating protein from Helicobacter pylori. J. Mol. Biol. 323(1):125-130.
Nishioka H, et al., 2003. The neutrophil-activating protein of Helicobacter pylori (HP-NAP) activates the MAPK pathway in human neutrophils. Eur. J. Immunol. 33(4):840-849.
Montecucco C, de Bernard M, 2003. Molecular and cellular mechanisms of action of the vacuolating cytotoxin (VacA) and neutrophil-activating protein (HP-NAP) virulence factors of Helicobacter pylori. Microbes Infect. 5(8):715-721.


OipA (outer inflammatory protein)  

Related genes: hopH;
Keywords: Proinflammatory effect;
Characteristics:
H. pylori-related gastritis is characterized by mucosal infiltration with neutrophils and mononuclear cells. The migration and activation of these cells is thought to be related to the local production of various proinflammatory cytokines, especially IL-8. The presence of a functional cag PAI is associated with increased IL-8 production. But it is not the sole H. pylori factor able to promote IL-8 secretion.
Regulated by slipped-strand repair mechanism (CT dinucleotide repeats in oipA gene).
Functions:
Involved in IL-8 production.
Mechanism:
Recent research indicates that OipA and the cag PAI are both necessary for full activation of the IL-8 promoter but act via different pathways that diverge upstream of IRF-1 where only OipA is involved in the STAT1-IRF1-ISRE pathway. The mucosal inflammatory response to H. pylori infection is complex and involves different pathways converging on the IL-8 promoter.
References:
Yamaoka Y, et al., 2000. A M(r) 34,000 proinflammatory outer membrane protein (oipA) of Helicobacter pylori. Proc. Natl. Acad. Sci. USA. 97(13):7533-7538.








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