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Helicobacter pylori Infection Induces Interleukin-18 Production in Gastric Epithelial (AGS) Cells

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Abstract

Helicobacter pylori colonization of the stomach results in a chronic–active gastritis characterized by mucosal infiltration of both neutrophils and lymphocytes. A T helper lymphocyte (Th1) profile predominates, which promotes the chronic and persistent inflammatory changes in the gastric mucosa in response to this bacterial pathogen. The cytokine interleukin-18 induces production of interferon-γ by activated T lymphocytes and promotes a Th1 profile. An in vitro model system was utilized to determine the role of interleukin-18 in response to infection of gastric epithelial cells by H. pylori. H. pylori isolates, characterized with respect to cagE and cagA and VacA status, were employed to infect AGS gastric epithelial cells. Interleukin-18 production was determined by immunoassay. Infection of AGS cells with H. pylori resulted in a 1.8-fold increase in interleukin-18 compared to uninfected cells (22.7 ± 2.4 vs. 12.7 ± 2.2 pg/ml; P&<0.005). This interleukin-18 response was independent of the cagE status of infecting strains (23.3 ± 1.9 vs. 26.3 ± 3.6 pg/ml; P = NS). Exposure of AGS cells to recombinant interleukin-18 resulted in dose-dependent and time-dependent secretion of interleukin-8 that was maximal following exposure to 100 pg/ml interleukin-18 for 24 hr (292 ± 5 pg/ml, versus 102 ± 14 pg/ml in unstimulated cells; P&<0.001). Interleukin-8 secretion was inhibited following pretreatment of cells with anti-interleukin-18 antibody and by pharmacological inhibition of the nuclear transcription factor, NF-κB. These findings demonstrate that interleukin-18 can enhance host chemokine response to H. pylori infection.

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Authors and Affiliations

  1. Research Institute, Hospital for Sick Children; Departments of Paediatrics, Physiology and Laboratory Medicine & Pathobiology, University of Toronto, Toronto, Ontario, Canada

    Bin Su, Peter J. M. Ceponis, Nicola L. Jones & Edwin Yau

  2. Sydney Children’s Hospital and School of Women’s and Children’s Health, University of New South Wales, Sydney, Australia

    Andrew S. Day, Daniel Sieveking & Philip M. Sherman

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  1. Andrew S. Day
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  2. Bin Su
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  3. Peter J. M. Ceponis
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  4. Nicola L. Jones
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  5. Edwin Yau
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  6. Daniel Sieveking
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  7. Philip M. Sherman
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Correspondence to Philip M. Sherman.

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Day, A.S., Su, B., Ceponis, P.J.M. et al. Helicobacter pylori Infection Induces Interleukin-18 Production in Gastric Epithelial (AGS) Cells. Dig Dis Sci 49, 1830–1835 (2004). https://doi.org/10.1007/s10620-004-9579-y

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  • DOI: https://doi.org/10.1007/s10620-004-9579-y

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