H. pylori Infection: Bacterial Virulence Factors and Cytokine Gene Polymorphisms as Determinants of Infection Outcome

References

• Morris Brown L.. Helicobacter pylori: Epidemiology and routes of transmission. Epidemiol Rev. 2000; 22: 283–97
   PubMed Web of Science ®Google Scholar
• Dunn B E, Cohen H, Blaser M J.. Helicobacter pylori. Clin Microbiol Rev. 1997; 10: 720–41
   PubMed Web of Science ®Google Scholar
• Montecucco C, Rappuoli R.. Living dangerously: How Helicobacter pylori survives in the human stomach. Nature Rev Mol Cell Biol. 2001; 2: 457–66
   PubMed Web of Science ®Google Scholar
• Plebani M, Basso D, Cassaro M, et al, Helicobacter pylori serology in patients with chronic gastritis. Am J Gastroenterol. 1996; 91: 954–8
   PubMed Web of Science ®Google Scholar
• Warburton V J, Everett S, Mapstone N P, et al, Clinical and histological associations of cagA and vacA genotypes in Helicobacter pylori gastritis. J Clin Pathol. 1998; 51: 55–61
   PubMed Web of Science ®Google Scholar
• Zambon C-F, Navaglia F, Basso D, Rugge M, Plebani M.. Helicobacter pylori babA2, cagA, and s1 vacA genes work synergistically in causing intestinal metaplasia. J Clin Pathol. 2003; 56: 287–91
   PubMed Web of Science ®Google Scholar
• Atherton J C, Peek R M, Tham K T, Cover T L, Blaser M J.. Clinical and pathological importance of heterogeneity in vacA, the vacuolating cytotoxin gene of Helicobacter pylori. Gastroenterology. 1997; 112: 92–9
   PubMed Web of Science ®Google Scholar
• Navaglia F, Basso D, Piva M G, et al, Helicobacter pylori cytotoxic genotype is associated with peptic ulcer and influences serology. Am J Gastroenterol. 1998; 93: 227–30
   PubMed Web of Science ®Google Scholar
• Basso D, Navaglia F, Brigato L, et al, Analysis of Helicobacter pylori vacA and cagA genotypes and serum antibody profile in benign and malignant gastroduodenal diseases. Gut. 1998; 43: 182–6
   PubMed Web of Science ®Google Scholar
• Yamaoka Y, Kodama T, Gutierrez O, et al, Relationship between Helicobacter pylori iceA, cagA, and vacA status and clinical outcome: Studies in four different countries. J Clin Microbiol. 1999; 37: 2274–9
   PubMed Web of Science ®Google Scholar
• Infection with Helicobacter pylori. IARC monographs on the evaluation of the carcinogenetic risks to humans. Vol. 61. Schistosomes, liver flukes and Helicobacter pylori. LyonFrance, International Agency for Research on Cancer, 1994; 177–241
   Google Scholar
• Blaser M J, Chyou P H, Nomura A.. Age at establishment of Helicobacter pylori infection and gastric adenocarcinoma, gastric ulcer, and duodenal ulcer risk. Cancer Res. 1995; 55: 562–5
   PubMed Web of Science ®Google Scholar
• Hirai M, Azuma T, Ito S, et al, High prevalence of neutralizing activity to Helicobacter pylori cytotoxin in serum of gastric-carcinoma patients. Int J Cancer. 1994; 56: 56–60
   PubMed Web of Science ®Google Scholar
• Blaser M J, Perez-Perez G I, Kleanthous H, et al, Infection with Helicobacter pylori strains possessing cagA is associated with an increased risk of developing adenocarcinoma of the stomach. Cancer Res. 1995; 55: 2111–5
   PubMed Web of Science ®Google Scholar
• Parsonnet J, Friedman G D, Orentreich N, Vogelman H.. Risk for gastric cancer in people with CagA positive or CagA negative Helicobacter pylori infection. Gut. 1997; 40: 297–301
   PubMed Web of Science ®Google Scholar
• Keates S, Keates A C, Warny M, et al, Differential activation of mitogen-activated protein kinases in AGS gastric epithelial cells by cag+ and cag− Helicobacter pylori. J Immunol. 1999; 163: 5552–9
   PubMed Web of Science ®Google Scholar
• Meyer-ter-Vehn T, Covacci A, Kist M, Pahl H L.. Helicobacter pylori activates mitogen-activated protein kinase cascades and induces expression of the proto-oncogens c-fos and c-jun. J Biol Chem. 2000; 275: 16064–72
   PubMed Web of Science ®Google Scholar
• Johnson G L, Lapadat R.. Mitogen-activated protein kinase pathways mediated by ERK, JNK, and p38 protein kinases. Science. 2002; 298: 1911–2
   PubMed Web of Science ®Google Scholar
• Peek R M, Jr, Moss S F, Tham K T, et al, Helicobacter pylori cagA+ strains and dissociation of gastric epithelial cell proliferation from apoptosis. J Natl Cancer Inst. 1997; 89: 863–8
   PubMedGoogle Scholar
• Peek R M, Jr.. Helicobacter pylori strain-specific modulation of gastric mucosal cellular turnover: Implications for carcinogenesis. J Gastroenterol. 2002; 37(Suppl 13): 10–6
   PubMed Web of Science ®Google Scholar
• Ho S B.. Premalignant lesions of the stomach. Sem Gastrointest Dis. 1996; 7: 61–73
   PubMedGoogle Scholar
• Bergin I L, Sheppard B J, Fox J G.. Helicobacter pylori infection and high dietary salt independently induce atrophic gastritis and intestinal metaplasia in commercially available outbred Mongolian gerbils. Dig Dis Sci. 2003; 48: 475–85
   PubMed Web of Science ®Google Scholar
• Moss S F, Calam J, Agarwal B, Wang S, Holt P R.. Induction of gastric epithelial apoptosis by Helicobacter pylori. Gut. 1996; 38: 498–501
   PubMed Web of Science ®Google Scholar
• Murakami K, Fujioka T, Kodama R, et al, Helicobacter pylori infection accelerates human gastric mucosal cell proliferation. J Gastreonterol. 1997; 32: 184–8
   PubMed Web of Science ®Google Scholar
• Rieder G, Hofmann J A, Hatz R A, Stolte M, Enders G A.. Up-regulation of inducible nitric oxide synthase in Helicobacter pylori-associated gastritis may represent an increased risk factor to develop gastric carcinoma of the intestinal type. Int J Med Microbiol. 2003; 293: 403–12
   PubMed Web of Science ®Google Scholar
• Baik S-C, Youn H-S, Chung M-H, et al, Increased oxidative DNA damage in Helicobacter pylori-infected human gastric mucosa. Cancer Res. 1996; 56: 1279–82
   PubMed Web of Science ®Google Scholar
• Farinati F, Cardin R, Degan P, et al, Oxidative DNA damage accumulation in gastric carcinogenensis. Gut. 1998; 42: 351–6
   PubMed Web of Science ®Google Scholar
• Farinati F, Cardin R, Russo V M, et al, Helicobacter pylori CagA status, mucosal oxidative damage and gastritis phenotype: A potential pathway to cancer?. Helicobacter. 2003; 8: 227–34
   PubMed Web of Science ®Google Scholar
• Basso D, Scrigner M, Toma A, et al, Helicobacter pylori infection enhances mucosal interleukin-1, interleukin-6, and the solubile receptor of interleukin-2. Int J Clin Lab Res. 1996; 26: 207–10
   PubMedGoogle Scholar
• Lindholm C, Quiding-Jarbrink M, Lonroth H, Hamlet A, Svennerholm A-M.. Local cytokine response in Helicobacter pylori-infected subjects. Infect Immun. 1998; 66: 5964–71
   PubMed Web of Science ®Google Scholar
• Zambon C-F, Basso D, Navaglia F, et al, Helicobacter pylori virulence genes and host IL-1RN and IL-1beta genes interplay in favouring the development of peptic ulcer and intestinal metaplasia. Cytokine. 2002; 18: 242–51
   PubMed Web of Science ®Google Scholar
• Holck S, Norgaard A, Bennedsen M, et al, Gastric mucosal cytokine responses in Helicobacter pylori-infected patients with gastritis and peptic ulcers. Association with inflammatory parameters and bacterial load. FEMS Immunol Med Microbiol. 2003; 36: 175–80
   PubMedGoogle Scholar
• Bontems P, Robert F, Van, Gossum A, Cadranel S, Mascart F.. Helicobacter pylori modulation of gastric and duodenal mucosal T cell cytokine secretion in children compared with adults. Helicobacter. 2003; 8: 216–26
   PubMed Web of Science ®Google Scholar
• El-Omar E M, Carrington M, Chow W-H, et al, Interleukin-1 polymorphisms associated with increased risk of gastric cancer. Nature. 2000; 404: 398–402
   PubMed Web of Science ®Google Scholar
• El-Omar E M, Carrington M, Chow W-H, et al, The role of interleukin-1 polymorphisms in the pathogenesis of gastric cancer. Nature. 2001; 412: 99
   PubMed Web of Science ®Google Scholar
• Machado J C, Pharoah P, Sousa S, et al, Interleukin 1B and interleukin 1RN polymorphisms are associated with increased risk of gastric carcinoma. Gastroenterology. 2001; 121: 823–9
   PubMed Web of Science ®Google Scholar
• Figueiredo C, Machado J C, Pharoah P, et al, Helicobacter pylori and interleukin 1 genotyping: An opportunity to identify high-risk individuals for gastric carcinoma. J Natl Cancer Inst. 2002; 94: 1680–7
   PubMed Web of Science ®Google Scholar
• Furuta T, El-Omar E M, Xiao F, et al, Interleukin 1β polymorphisms increase risk of hypochloridria and atrophic gastritis and reduce risk of duodenal ulcer recurrence in Japan. Gastroenterology. 2002; 123: 92–105
   PubMed Web of Science ®Google Scholar
• Machado J C, Figueiredo C, Canedo P, et al, A proinflammatory genetic profile increases the risk for chronic atrophic gastritis and gastric carcinoma. Gastroenterology. 2003; 125: 364–71
   PubMed Web of Science ®Google Scholar
• El-Omar E M, Rabkin C S, Gammon M D, et al, Increased risk of noncardia gastric cancer associated with proinflammatory cytokine gene polymorphisms. Gastroenterology. 2003; 124: 1193–201
   PubMed Web of Science ®Google Scholar
• Zeng Z-R, Hu P-J, Hu S, et al, Association of interleukin 1B gene polymorphisms and gastric cancers in high and low prevalence regions in China. Gut. 2003; 52: 1684–9
   PubMed Web of Science ®Google Scholar
• Mobley H LT, Island M D, Hausinger R P.. Molecular biology of microbial ureases. Microbiol Rev. 1995; 59: 451–80
   PubMedGoogle Scholar
• Marais A, Mendz G L, Hazell S L, Mégraud F.. Metabolism and genetics of Helicobacter pylori: The genome era. Microbiol Mol Biol Rev. 1999; 63: 642–74
   PubMed Web of Science ®Google Scholar
• Voland P, Weeks D L, Marcus E A, et al, Interactions among the seven Helicobacter pylori proteins encoded by the urease gene cluster. Am J Physiol Gastrointest Liver Physiol. 2003; 284: G96–106
   Web of Science ®Google Scholar
• Scott D R, Weeks D, Hong C, et al, The role of internal urease in acid resistance of Helicobacter pylori. Gastroenterology. 1998; 114: 58–70
   PubMed Web of Science ®Google Scholar
• Dunn B E, Phadnis S H.. Structure, function and localization of Helicobacter pylori urease. Yale J Biol Med. 1998; 71: 63–73
   PubMed Web of Science ®Google Scholar
• Sachs G, Shin J M, Munson K, et al, Review article: The control of gastric acid and Helicobacter pylori eradication. Aliment Pharmacol Ther. 2000; 14: 1383–401
   PubMed Web of Science ®Google Scholar
• Sachs G, Shin J M, Vagin O, et al, Current trends in treatment of upper gastrointestinal disease. Best Pract Res Clin Gastroenterol. 2002; 16: 835–49
   PubMed Web of Science ®Google Scholar
• Hong W, Sano K, Morimatsu S, et al, Medium pH-dependent redistribution of the urease of Helicobacter pylori. J Med Microbiol. 2003; 52: 211–6
   PubMed Web of Science ®Google Scholar
• Stingl K, Altendorf K, Bakker E P.. Acid survival of Helicobacter pylori: How does urease activity trigger cytoplasmic pH homeostasis?. Trends Microbiol. 2002; 10: 70—4
   PubMed Web of Science ®Google Scholar
• Tanahashi T, Kita M, Kodama T, et al, Cytokine expression and production by purified Helicobacter pylori urease in human gastric epithelial cells. Infect Immun. 2000; 68: 664–71
   PubMed Web of Science ®Google Scholar
• Berger A.. Helicobacter pylori breath test. Br Med J. 2002; 324: 1263
   PubMedGoogle Scholar
• Basso D, Navaglia F, Cassaro M, et al, Gastric juice polymerase chain reaction: An alternative to histology in the diagnosis of Helicobacter pylori infection. Helicobacter. 1996; 1: 159–64
   PubMedGoogle Scholar
• Zambon C-F, Basso D, Navaglia F, et al, Non-invasive diagnosis of Helicobacter pylori infection: Simplified 13C-urea breath test, stool antigen testing or DNA PCR in human faeces in a clinical laboratory setting?. Clin Biochem. 2004; 37: 261–7
   PubMed Web of Science ®Google Scholar
• Yamaoka Y, Kodama T, Kashima K, Graham D Y, Sepulveda A R.. Variants of the 3′ region of the cagA gene in Helicobacter pylori isolates from patients with different H. pylori-associated diseases. J Clin Microbiol. 1998; 36: 2258–63
   PubMed Web of Science ®Google Scholar
• Yamaoka Y, El-Zimaity H M, Gutierrez O, et al, Relationship between the cagA 3′ repeat region of Helicobacter pylori, gastric histology, and susceptibility to low pH. Gastroenterology. 1999; 117: 342–9
   PubMed Web of Science ®Google Scholar
• Censini S, Lange C, Xiang Z, et al, cag, a pathogenicity island of Helicobacter pylori, encodes type I-specific and disease-associated virulence factors. Proc Natl Acad Sci USA. 1996; 93: 14648–53
   PubMed Web of Science ®Google Scholar
• Covacci A, Rappuoli R.. Tyrosine-phosphorylated bacterial proteins: Trojan horses for the host cell. J Exp Med. 2000; 191: 587–92
   PubMedGoogle Scholar
• Salama N, Guillemin K, McDaniel T K, et al, A whole-genome microarray reveals genetic diversity among Helicobacter pylori strains. Proc Natl Acad Sci USA. 2000; 97: 14668–73
   PubMed Web of Science ®Google Scholar
• Segal E D, Cha J, Lo J, Falkow S, Tompkins L S.. Altered state: Involvement of phosphorylated CagA in the induction of host cellular growth changes by Helicobacter pylori. Proc Natl Acad Sci USA. 1999; 96: 14559–64
   PubMed Web of Science ®Google Scholar
• Stein M, Rappuoli R, Covacci A.. Tyrosine phosphorylation of the Helicobacter pylori CagA antigen after cag-driven host cell translocation. Proc Natl Acad Sci USA. 2000; 97: 1263–8
   PubMed Web of Science ®Google Scholar
• Cox J M, Clayton C L, Tomita T, et al, cDNA array analysis of cag pathogenicity island-associated Helicobacter pylori epithelial cell response genes. Infect Immun. 2001; 69: 6970–80
   PubMed Web of Science ®Google Scholar
• Higashi H, Tsutsumi R, Fujita A, et al, Biological activity of the Helicobacter pylori virulence factor CagA is determined by variation in the tyrosine phosphorylation sites. Proc Natl Acad Sci USA. 2002; 99: 14428–33
   PubMed Web of Science ®Google Scholar
• Guillemin K, Salama N R, Tompkins L S, Falkow S.. cag pathogenicity island-specific responses of gastric epithelial cells to Helicobacter pylori infection. Proc Natl Acad Sci USA. 2002; 99: 15136–41
   PubMed Web of Science ®Google Scholar
• Higashi H, Tsutsumi R, Muto S, et al, SHP-2 tyrosine phosphatase as an intracellular target of Helicobacter pylori CagA protein. Science. 2002; 295: 683–6
   PubMed Web of Science ®Google Scholar
• Higashi H, Nakaya A, Tsutsumi R, et al, Helicobacter pylori CagA induces Ras-independent morphogenetic response through SHP-2 recruitment and activation. J Biol Chem. 2004; 279: 17205–16
   PubMed Web of Science ®Google Scholar
• Choi I J, Kim J S, Kim J M, Jung H C, Song I S.. Effect of inhibition of extracellular signal-regulated kinase 1 and 2 pathway on apoptosis and bcl-2 expression in Helicobacter pylori-infected AGS cells. Infect Immun. 2003; 71: 830–7
   PubMed Web of Science ®Google Scholar
• Hirata Y, Maeda S, Mitsuno Y, et al, Helicobacter pylori CagA protein activates serum response element-driven transcription independently of tyrosine phosphorylation. Gastroenterology. 2002; 123: 1962–71
   PubMed Web of Science ®Google Scholar
• Amieva M R, Vogelmann R, Covacci A, et al, Disruption of the epithelial apical-junctional complex by Helicobacter pylori CagA. Science. 2003; 300: 1430–4
   PubMed Web of Science ®Google Scholar
• Moss S F, Sordillo E M, Abdalla A M, et al, Increased gastric epithelial cell apoptosis associated with colonization with cagA+ Helicobacter pylori strains. Cancer Res. 2001; 61: 1406–11
   PubMed Web of Science ®Google Scholar
• Selbach M, Moese S, Mayer T F, Backert S.. Functional analysis of the Helicobacter pylori cag pathogenicity island reveals both VirD4-CagA-dependent and VirD4-CagA-independent mechanisms. Infect Immun. 2002; 70: 665–71
   PubMed Web of Science ®Google Scholar
• Sharma S A, Tummuru M KR, Blaser M J, Kerr L D.. Activation of IL-8 gene expression by Helicobacter pylori is regulated by transcription factor nuclear factor-kB in gastric epithelial cells. J Immunol. 1998; 160: 2401–7
   PubMed Web of Science ®Google Scholar
• Israel D A, Peek R M.. Review article: Pathogenesis of Helicobacter pylori-induced gastric inflammation. Aliment Pharmacol Ther. 2001; 15: 1271–90
   PubMed Web of Science ®Google Scholar
• Papini E, Zoratti M, Cover T L.. In search of the Helicobacter pylori VacA mechanism of action. Toxicon. 2001; 39: 1757–67
   PubMed Web of Science ®Google Scholar
• Montecucco C, de, Bernard M.. Molecular and cellular mechanisms of action of the vacuolating cytotoxin (VacA) and neutrophil-activating protein (HP-NAP) virulence factors of Helicobacter pylori. Microbes Infect. 2003; 5: 715–21
   PubMed Web of Science ®Google Scholar
• Cover T L, Krishna U S, Israel D A, Peek R M.. Induction of gastric epithelial cell apoptosis by Helicobacter pylori vacuolating cytotoxin. Cancer Res. 2003; 63: 951–7
   PubMed Web of Science ®Google Scholar
• Supajatura V, Ushio H, Wada A, et al, Cutting edge: VacA, a vacuolating cytotoxin of Helicobacter pylori, directly activates mast cells for migration and production of proinflammatory cytokines. J Immunol. 2002; 168: 2603–7
   PubMed Web of Science ®Google Scholar
• Plebani M, Basso D, Busatto G, et al, Are tryptase and cathepsin D related to Helicobacter pylori infection and mucosal gastrin in peptic ulcer?. Res Exp Med. 1994; 194: 1–8
   PubMedGoogle Scholar
• Gebert B, Fischer W, Weiss E, Hoffmann R, Haas R.. Helicobacter pylori vacuolating cytotoxin inhibits T lymphocyte activation. Science. 2003; 301: 1099–1102
   PubMed Web of Science ®Google Scholar
• Yamaoka Y, Kwon D H, Graham D Y.. A Mr 34,000 proinflammatory outer membrane protein (oipA) of Helicobacter pylori. Proc Natl Acad Sci USA. 2000; 97: 7533–8
   PubMed Web of Science ®Google Scholar
• Yamaoka Y, Kikuchi S, El-Zimaity H MT, et al, Importance of Helicobacter pylori oipA in clinical presentation, gastric inflammation, and mucosal interleukin 8 production. Gastroenterology. 2002; 123: 414–24
   PubMed Web of Science ®Google Scholar
• Coskun T, Chu S, Montrose M H.. Intragastric pH regulates conversion from net acid to net alkaline secretion by the rat stomach. Am J Physiol Gastrointest Liver Physiol. 2001; 281: G870–7
   Web of Science ®Google Scholar
• Coskun T, Baumgartner H K, Chu S, Montrose M H.. Coordinated regulation of gastric chloride secretion with both acid and alkali secretion. Am J Physiol Gastrointest Liver Physiol. 2002; 283: G1147–55
   Web of Science ®Google Scholar
• Baumgartner H K, Montrose M H.. Regulated alkali secretion acts in tandem with unstirred layers to regulate mouse gastric surface pH. Gastroenterology. 2004; 126: 774–83
   PubMed Web of Science ®Google Scholar
• Evans D J, Evans D G.. Helicobacter pylori adhesins: Review and perspectives. Helicobacter. 2000; 5: 183–95
   PubMed Web of Science ®Google Scholar
• Ilver D, Arnqvist A, Ogren J, et al, Helicobacter pylori adhesin binding fucosylated histo-blood group antigens revealed by retagging. Science. 1998; 279: 373–7
   PubMed Web of Science ®Google Scholar
• Prinz C, Schoniger M, Rad R, et al, Key importance of the Helicobacter pylori adherence factor blood group antigen binding adhesin during chronic gastric inflammation. Cancer Res. 2001; 61: 1903–9
   PubMed Web of Science ®Google Scholar
• Yamaoka Y, Souchek J, Odenbreit S, et al, Discrimination between cases of duodenal ulcer and gastritis on the basis of putative virulence factors of Helicobacter pylori. J Clin Microbiol. 2002; 40: 2244–6
   PubMed Web of Science ®Google Scholar
• Yu J, Leung W K, Go M YY, et al, Relationship between Helicobacter pylori babA2 status with gastric epithelial cell turnover and premalignant gastric lesions. Gut. 2002; 51: 480–4
   PubMed Web of Science ®Google Scholar
• Mahdavi J, Sondén B, Hurting M, et al, Helicobacter pylori SabA adhesin in persistent infection and chronic inflammation. Science. 2002; 297: 573–8
   PubMed Web of Science ®Google Scholar
• Sheu B-S, Sheu S-M, Yang H-B, Huang A-H, Wu J-J. Host gastric Lewis expression determines the bacterial density of Helicobacter pylori in babA2 genopositive infection. Gut. 2003; 52: 927–32
   PubMed Web of Science ®Google Scholar
• Cao P, Cover T L.. Two different families of hopQ alleles in Helicobacter pylori. J Clin Microbiol. 2002; 40: 4504–11
   PubMed Web of Science ®Google Scholar
• Suerbaum S, Michetti P.. Helicobacter pylori infection. N Engl J Med. 2002; 347: 1175–86
   PubMed Web of Science ®Google Scholar
• Sutton P, Kolesnikow T, Danon S, Wilson J, Lee A.. Dominant nonresponsiveness to Helicobacter pylori infection is associated with production of interleukin 10 but not gamma interferon. Infect Immun. 2000; 68: 4802–4
   PubMed Web of Science ®Google Scholar
• Neurath M F, Finotto S, Glimcher L H.. The role of Th1/Th2 polarization in mucosal immunity. Nature Med. 2002; 8: 567–73
   PubMed Web of Science ®Google Scholar
• Bauditz J, Ortner M, Bierbaum M, et al, Production of IL-12 in gastritis relates to infection with Helicobacter pylori. Clin Exp Immunol. 1999; 117: 316–23
   PubMed Web of Science ®Google Scholar
• Hida N, Shimoyama T Jr, Neville P, et al, Increased expression of IL-10 and IL-12 (p40) mRNA in Helicobacter pylori infected gastric mucosa: Relation to bacterial cag status and peptic ulceration. J Clin Pathol. 1999; 52: 658–64
   PubMed Web of Science ®Google Scholar
• Guiney D G, Hasegawa P, Cole S P.. Helicobacter pylori preferentially induces interleukin 12 (IL-12) rather than IL-6 or IL-10 in human dendritic cells. Infect Immun. 2003; 71: 4163–6
   PubMed Web of Science ®Google Scholar
• Weigmann B, Neurath M F.. T-bet and mucosal Th1 responses in the gastrointestinal tract. Gut. 2002; 51: 301–3
   PubMed Web of Science ®Google Scholar
• Trinchieri G.. Interleukin-12 and the regulation of innate resistance and adaptive immunity. Nature Rev Immunol. 2003; 3: 133–46
   PubMed Web of Science ®Google Scholar
• D'Elios M M, Manghetti M, De, Carli M, et al, T helper 1 effector cells specific for Helicobacter pylori in the gastric antrum of patients with peptic ulcer disease. J Immunol. 1997; 158: 962–67
   PubMed Web of Science ®Google Scholar
• Akhiani A A, Pappo J, Kabok Z, et al, Protection against Helicobacter pylori infection following immunization is IL-12-dependent and mediated by Th1 cells. J Immunol. 2002; 169: 6977–84
   PubMed Web of Science ®Google Scholar
• Skoog T, van't Hooft F M, Kallin B, et al, A common functional polymorphism (C→A substitution at position −863) in the promoter region of the tumor necrosis factor-α (TNF-α) gene associated with reduced circulating levels of TNF-α. Hum Mol Genet. 1999; 8: 1443–9
   PubMed Web of Science ®Google Scholar
• Pravica V, Perrey C, Stevens A, Lee J-H. Hutchinson IV. A single nucleotide polymorphism in the first intron of the human IFN-γ gene: Absolute correlation with a polymorphic CA microsatellite marker of high IFN-γ production. Hum Immunol. 2000; 61: 863–6
   PubMed Web of Science ®Google Scholar
• Hacker U T, Erhardt S, Tschop K, Jelinek T, Endres S.. Influence of the IL-1Ra polymorphism on in vivo synthesis of the IL-1Ra and IL-1β after live yellow fever vaccination. Clin Exp Immunol. 2001; 125: 465–9
   PubMed Web of Science ®Google Scholar
• Hwang I-R, Kodama T, Kikuchi S, et al, Effect of interleukin 1 polymorphisms on gastric mucosal interleukin 1β production in Helicobacter pylori infection. Gastroenterology. 2002; 123: 1793–1803
   PubMed Web of Science ®Google Scholar
• Furuta T, Shirai N, Takashima M, Xiao F, Sugimura H.. Effect of genotypic differences in interleukin-1 beta on gastric acid secretion in Japanese patients infected with Helicobacter pylori. Am J Med. 2002; 112: 141–3
   PubMed Web of Science ®Google Scholar
• Hoogendoorn B, Coleman S L, Guy C A, et al, Functional analysis of human promoter polymorphisms. Hum Mol Genet. 2003; 12: 2249–54
   PubMed Web of Science ®Google Scholar
• Zambon C-F, Basso D, Navaglia F, et al, Increased risk of noncardia gastric cancer associated with proinflammatory cytokine gene polymorphisms. Gastroenterology. 2004; 126: 382–3
   PubMed Web of Science ®Google Scholar
• Ando T, Kusugami K, Ohsuga M, et al, Mucosal macrophage inflammatory protein-1α levels are increased in Helicobacter pylori infection. J Clin Gastroenterol. 1998; 27(Suppl. 1): S144–9
   Web of Science ®Google Scholar
• Nozawa Y, Nishihara K, Peek R M, et al, Identification of a signaling cascade for interleukin-8 production by Helicobacter pylori in human gastric epithelial cells. Biochem Pharmacol. 2002; 64: 21–30
   PubMed Web of Science ®Google Scholar
• El-Omar E M.. The importance of interleukin 1β in Helicobacter pylori associated disease. Gut. 2001; 48: 743–7
   PubMed Web of Science ®Google Scholar
• Beales I LP.. Effect of interleukin-1β on proliferation of gastric epithelial cells in culture. BMC Gastroenterology. 2002; 2: 7
   PubMedGoogle Scholar
• Beales I LP, Calam J.. Interleukin 1β and tumour necrosis factor a inhibit acid secretion in cultured rabbit parietal cells by multiple pathways. Gut. 1998; 42: 227–34
   PubMed Web of Science ®Google Scholar
• Takashima M, Furuta T, Hanai H, Sugimura H, Kaneko E.. Effects of Helicobacter pylori infection on gastric acid secretion and serum gastrin levels in Mongolian gerbils. Gut. 2001; 48: 765–73
   PubMed Web of Science ®Google Scholar
• Mahr S, Neumayer N, Gerhard M, et al, IL-1 beta-induced apoptosis in rat gastric enterochromaffin-like cells is mediated by iNOS, NK-kappaB, and Bax protein. Gastroenterology. 2000; 118: 515–24
   PubMed Web of Science ®Google Scholar
• Weigert N, Schaffer K, Schusdziarra V, et al, Gastrin secretion from primary cultures of rabbit antral G cells: Stimulation by inflammatory cytokines. Gastroenterology. 1996; 110: 147–54
   PubMed Web of Science ®Google Scholar
• Wolfe M M, Nompleggi D J.. Cytokine inhibition of gastric acid secretion—a little goes a long way. Gastroenterology. 1992; 102: 2177–8
   PubMedGoogle Scholar
• Arend W P.. The balance between IL-1 and IL-1Ra in disease. Cytokine Growth Factor Rev. 2002; 13: 323–40
   PubMed Web of Science ®Google Scholar
• Balkwill F.. Tumor necrosis factor or tumor promoting factor?. Cytokine Growth Factor Rev. 2002; 13: 135–41
   PubMed Web of Science ®Google Scholar
• Thalmaier U, Lehn N, Pfeffer K, et al, Role of tumor necrosis factor alpha in Helicobacter pylori gastritis in tumor necrosis factor receptor 1-deficient mice. Infect Immun. 2002; 70: 3149–55
   PubMed Web of Science ®Google Scholar
• van den, Brink G R, ten Kate F J, Ponsioen C Y, et al, Expression and activation of NF-kB in the antrum of the human stomach. J Immunol. 2000; 164: 3353–9
   PubMed Web of Science ®Google Scholar
• Huber C, Zanner R, Pohlinger A, et al, Tumor necrosis factor-alpha effects on rat gastric enterochromaffin-like cells. Digestion. 2002; 65: 87–102
   PubMed Web of Science ®Google Scholar
• Beales I LP, Post L, Calam J, Yamada T, Del, Valle J.. Tumor necrosis factor alpha stimulates gastrin release from canine and human antral G cells: Possible mechanism of the Helicobacter pylori-gastrin link. Eur J Clin Invest. 1996; 26: 609–11
   PubMed Web of Science ®Google Scholar
• Kunstmann E, Epplen C, Elitok E, et al, Helicobacter pylori infection and polymorphisms in the tumor necrosis factor region. Electrophoresis. 1999; 20: 1756–61
   PubMed Web of Science ®Google Scholar
• Yea S S, Yang Y-I, Jang W H, et al, Association between TNF-α promoter polymorphism and Helicobacter pylori cagA subtype infection. J Clin Pathol. 2001; 54: 703–6
   PubMed Web of Science ®Google Scholar
• Jang W H, Yang Y-I, Yea S S, et al, The −238 tumor necrosis factor-α promoter polymorphism is associated with decreased susceptibility to cancers. Cancer Lett. 2001; 166: 41–6
   PubMed Web of Science ®Google Scholar
• Knight J C, Udalova I, Hill A VS, et al, A polymorphism that affects OCT-1 binding to the TNF promoter region is associated with severe malaria. Nat Genet. 1999; 22: 145–50
   PubMed Web of Science ®Google Scholar
• Hohjoh H, Tokunaga K.. Allele specific binding of ubiquitous transcription factor OCT-1 to the functional single nucleotide polymorphism (SNP) sites in the tumor necrosis factor-alpha gene (TNFA) promoter. Genes Immun. 2001; 2: 105–9
   PubMed Web of Science ®Google Scholar
• van, Heel D A, Udalova I A, De, Silva A P, et al, Inflammatory bowel disease is associated with a TNF polymorphism that affects an interaction between the OCT1 and NF-kB transcription factors. Hum Mol Genet. 2002; 11: 1281–9
   PubMed Web of Science ®Google Scholar
• Kroeger K M, Steer J H, Joyce D A, Abraham L J.. Effects of stimulus and cell type on the expression of the −308 tumour necrosis factor promoter polymorphism. Cytokine. 2000; 12: 110–19
   PubMed Web of Science ®Google Scholar
• de, Jong B A, Westendorp R GJ, Bakker A M, Huizinga TWJ.. Polymorphisms in or near tumor necrosis factor (TNF)-gene do not determine levels of endotoxin-induced TNF production. Genes Immun. 2002; 3: 25–9
   PubMed Web of Science ®Google Scholar
• Shtrichman R, Samuel C E.. The role of gamma interferon in antimicrobial immunity. Curr Opin Microbiol. 2001; 4: 251–9
   PubMed Web of Science ®Google Scholar
• Sawai N, Kita M, Kodama T, et al, Role of gamma interferon in Helicobacter pylori-induced gastric inflammatory responses in a mouse model. Infect Immun. 1999; 67: 279–85
   PubMed Web of Science ®Google Scholar
• Obonyo M, Guiney D G, Harwood J, Fierer J, Cole S P.. Role of gamma interferon in Helicobacter pylori induction of inflammatory mediators during murine infection. Infect Immun. 2002; 70: 3295–9
   PubMed Web of Science ®Google Scholar
• Thye T, Burchard G D, Nilius M, Muller-Myhsok B, Horstmann R D.. Genome-wide linkage analysis identifies polymorphisms in the human interferon-g receptor affecting Helicobacter pylori infection. Am J Hum Genet. 2003; 72: 448–53
   PubMed Web of Science ®Google Scholar
• Julinger S, Bongartz M, Luty A JF, Kremsner P G, Kun JFJ.. Functional analysis of a promoter variant of the gene encoding the interferon-gamma receptor chain I. Immunogenetics. 2003; 54: 675–80
   PubMed Web of Science ®Google Scholar
• Chen W, Shu D, Chadwick S.. Helicobacter pylori infection: Mechanism of colonization and functional dyspepsia. Reduced colonization of gastric mucosa by Helicobacter pylori in mice deficient in interleukin-10. J Gastroenterol Hepatol. 2001; 16: 377–83
   PubMed Web of Science ®Google Scholar
• Turner D M, Williams D M, Sankaran D, et al, An investigation of polymorphism in the interleukin-10 gene promoter. Eur J Immunogenet. 1997; 24: 1–8
   PubMedGoogle Scholar
• Hwang I-R, Hsu P-I, Peterson L E, et al, Interleukin-6 genetic polymorphisms are not related to Helicobacter pylori-associated gastroduodenal diseases. Helicobacter. 2003; 8: 142–8
   PubMed Web of Science ®Google Scholar
• Hamajima N, Katsuda N, Matsuo K, et al, High anti-Helicobacter pylori antibody seropositivity associated with a combination of IL-8–251 TT and IL-10–819 TT genotypes. Helicobacter. 2003; 8: 105–10
   PubMed Web of Science ®Google Scholar