Duodenal ulcer promoting gene of Helicobacter pylori

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Duodenal ulcer promoting gene of Helicobacter pylori Hong Lu, Ping-I. Hsu, David Y. Graham, Yoshio Yamaoka Gastroenterology Volume 128, Issue 4, Pages 833-848 (April 2005) DOI: 10.1053/j.gastro.2005.01.009 Copyright © 2005 American Gastroenterological Association Terms and Conditions

Figure 1 Univariate analysis showing the relationship between the jhp0917-0918 gene (dupA) and the gastric mucosal histology. The scores (0: absent/normal to 5: maximal intensity) for neutrophil infiltration, intestinal metaplasia, and atrophy scores are presented separately in relation to clinical presentation in 1 East Asian and 1 Western country (Japan and Colombia, respectively). The strains from Japanese patients included 34 dupA-positive strains (7 from gastritis, 11 from DU, 13 from GU, and 3 from gastric cancer) and 124 dupA-negative strains (42 from gastritis, 19 from DU, 37 from GU, and 26 from gastric cancer). Strains from Colombia included 50 dupA-positive strains (14 from gastritis, 21 from DU, 9 from GU, and 6 from gastric cancer) and 87 dupA-negative strains (22 from gastritis, 17 from DU, 15 from GU, and 33 from gastric cancer). The data are expressed as mean ± standard error. Gastroenterology 2005 128, 833-848DOI: (10.1053/j.gastro.2005.01.009) Copyright © 2005 American Gastroenterological Association Terms and Conditions

Figure 2 In vivo gastric mucosal IL-8 levels and the jhp0917-0918 status. Mucosal IL-8 levels from biopsy specimens measured by ELISA are presented on the left panel, and adjusted IL-8 levels for H pylori density (IL-8 per H pylori) are presented on the right panel. IL-8 in the supernatant was assayed in duplicate. Data are expressed as mean ± standard error. Gastroenterology 2005 128, 833-848DOI: (10.1053/j.gastro.2005.01.009) Copyright © 2005 American Gastroenterological Association Terms and Conditions

Figure 3 Schematic structure of the jhp0917 gene and jhp0918 gene in strain J99 and that of the dupA gene in the clinical isolates. All 24 clinical isolates examined contains “C or T” insertion after position 1385 to produce 1 continuous open-reading frame homologue to the virB4 gene. We denote the gene containing the sequences of the jhp0917 gene and jhp0918 as the duodenal ulcer-promoting (dupA) gene. Gastroenterology 2005 128, 833-848DOI: (10.1053/j.gastro.2005.01.009) Copyright © 2005 American Gastroenterological Association Terms and Conditions

Figure 4 In vitro IL-8 production from MKN45 cells cocultured with wild-type strain C142 and its dupA-deleted mutant and dupA-complemented mutant and clinical isolates is shown. H pylori (MOI of 100) was cocultured with MKN45 cells for 20 hours. Experiments were performed at least 4 times for the wild type and its isogenic mutants and were performed in duplicate for clinical samples. IL-8 in the supernatant was assayed by an ELISA in duplicate. Data are expressed as mean ± standard error. Gastroenterology 2005 128, 833-848DOI: (10.1053/j.gastro.2005.01.009) Copyright © 2005 American Gastroenterological Association Terms and Conditions

Figure 5 Shows the luciferase reporter activity of ISRE, NF-κB, AP-1, and CRE associated with H pylori infection. Luciferase reporter gene assay was performed as previously described 35 at least 4 times for (A) wild type and its isogenic mutant and was performed in duplicate for (B) clinical samples. Luciferase activity was normalized by renilla luciferase vector DNA (Promega), and normalized luciferase activity (fold induction) is presented. Data are expressed as mean ± standard error of normalized luciferase activity. Gastroenterology 2005 128, 833-848DOI: (10.1053/j.gastro.2005.01.009) Copyright © 2005 American Gastroenterological Association Terms and Conditions

Figure 6 Susceptibility of H pylori to exposure to low pH. Log10 kill represents the difference in viable H pylori before and after exposure to low pH. Assays were performed at least 4 times. Data are expressed as mean ± standard error. Gastroenterology 2005 128, 833-848DOI: (10.1053/j.gastro.2005.01.009) Copyright © 2005 American Gastroenterological Association Terms and Conditions