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b receptor for Helicobacter pylori in their gastric epithelium had increased attachment of H. pylori after inoculation, production of autoantibodies to Lewis antigens on both the bacteria and parietal cells, and increased gastritis and parietal cell loss.
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29 Aihara M, Tsuchimoto D, Takizawa H, Azuma A, Wakebe H, Ohmoto Y, et al.: Mechanisms involved in Helicobacter pylori-induced interleukin-8 production by a gastric cancer cell line, MKN45. Infect Immun 1997, 65:3218-3224.
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30 Sharma SA, Tummuru MK, Blaser MJ, Kerr LD: Activation of IL-8 gene expression by Helicobacter pylori is regulated by transcription factor nuclear factor-kappa B in gastric epithelial cells. J Immunol 1998, 160:2401-2407. cagA+ strains were reported to induce increased binding activity of the transcription factor NF-κB to the IL-8 promoter and hence increased IL-8 gene expression. NF-κb mediated IL-8 transcription is suggested as a mechanism for the increased gastric inflammation that occurs with infection with cagA+ Helicobacter pylori strains.
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33 Segal ED, Lange C, Covacci A, Tompkins LS, Falkow S: Induction of host signal transduction pathways by Helicobacter pylori. Proc Natl Acad Sci U S A 1997, 94:7595-7599. This group has previously demonstrated that adherence of Helicobacter pylori to gastric epithelial cells is associated with attaching and effacing lesions, cytoskeletel rearrangements, and tyrosine phosphorylantion of host cell proteins similar to those occuring with enteropathogenic Esherichia coli. In this report, mutations in cag pathogenicity island genes are shown to abolish tyrosine phosphorylation and IL-8 synthesis but not cytoskeletal rearrangements. In addition a tyrosine phosphorylation-independent pathway of IL-8 production was identified.
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Helicobacter pylori culture supernatant interferes with epidermal growth factor-activated signal transduction in human gastric KATO III cells
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34 Pai R, Wyle FA, Cover TL, Itani RM, Domek MJ, Tarnawski AS: Helicobacter pylori culture supernatant interferes with epidermal growth factor-activated signal transduction in human gastric KATO III cells. Am J Pathol 1998, 152:1617-1624.
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Helicobacter pylori upregulates expression of epidermal growth factor-related peptides, but inhibits their proliferative effect in MKN 28 gastric mucosal cells
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35 Romano M, Ricci V, Di Popolo A, Sommi P, Del Vecchio Blanco C, Bruni CB, et al.: Helicobacter pylori upregulates expression of epidermal growth factor-related peptides, but inhibits their proliferative effect in MKN 28 gastric mucosal cells. J Clin Invest 1998, 101:1604-1613. EGF and related growth factors are important in gastric mucosal cytoprotection and healing. In this study, Helicobacter pylori suspensions or culture supernatants were found to increase gene expression of amphiregulin and heparin-binding EGF-like growth factor. However, epithelial cell growth stimulation by these proteins was abolished by H. pylori culture filtrates. This inhibitory effect was independent of effects on the EGF receptor. The ability of H. pylori to block the effects of EGF-related growth factors may have a central role in H. pylori-induced mucosal injury.
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36
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Helicobacter pylori disrupts epithelial barrier function in a process inhibited by protein kinase C activators
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36 Terres AM, Pajares JM, Hopkins AM, Murphy A, Moran A, Baird AW, Kelleher D: Helicobacter pylori disrupts epithelial barrier function in a process inhibited by protein kinase C activators. Infect Immun 1998, 66:2943-2950. In this in vitro study, H. pylori sonicates were shown to decrease epithelial permeability in monolayers of intestinal epithelial cells. This alteration in barrier function may represent a mechanism by which H. pylori antigens can reach the gastric lamina propria.
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Apoptosis in gastric epithelial cells is induced by Helicobacter pylori and accompanied by increased expression of BAK
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37 Chen G, Sordillo EM, Ramey WG, Reidy J, Holt PR, Krajewski S, et al.: Apoptosis in gastric epithelial cells is induced by Helicobacter pylori and accompanied by increased expression of BAK. Biochem Biophys Res Commun 1997, 239:626-632. This study demonstrated that Helicobacter pylori induces apoptosis in a gastric epithelial cell line (AGS cells) in a concentration-dependent manner. This induction required bacterial-epithelial cell contact and appeared to also be dependent on expression of the Bcl-2 family protein Bak. Increased expression of Bak was also demonstrated in the epithelial cells in the superficial two thirds of gastric glands of H. pylori-infected human gastric tissue.
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40 Fan X, Crowe SE, Behar S, Gunasena H, Ye G, Haeberle H, et al.: The effect of class II major histocompatibility complex expression on adherence of Helicobacter pylori and induction of apoptosis in gastric epithelial cells: a mechanism for T helper cell type 1-mediated damage. J Exp Med 1998, 187:1659-1669. This study demonstrates that Helicobacter pylori-stimulated apoptosis may occur by H. pylori binding to class II MHC molecules on gastric epithelial cells and subsequent signaling events.
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43 Haeberle HA, Kubin M, Bamford KB, Garofalo R, Graham DY, El-Zaatari F, et al.: Differential stimulation of interleukin-12 (IL-12) and IL-10 by live and killed Helicobacter pylori in vitro and association of IL-12 production with gamma interferon-producing T cells in the human gastric mucosa. Infect Immun 1997, 65:4229-4235. In gastric biopsy specimens, no differences in expression of IL-10 and IL-12 were observed between tissues infected or uninfected with Helicobacter pylori. However, stimulation of peripheral blood mononuclear cells with H. pylori demonstrated that live H. pylori induced much greater increases of IL-12 than of IL-10. Killed H. pylori stimulated significantly higher levels of IL-10 than did live bacteria. These results support the concept of a Th1-predominant response to live bacteria, because IL-12 selects for Th1 cells and stimulates interferon-γ production, and also suggest that killed preparations or other components used in oral vaccines may be useful in inducing Th2 responses.
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