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Differential Effects of Multiplicity of Infection on Helicobacter pylori-Induced Signaling Pathways and Interleukin-8 Gene Transcription

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Abstract

Interleukin-8 (IL-8) plays a central role in the pathogenesis of Helicobacter pylori infection. We used four different H. pylori strains isolated from patients with gastritis or duodenal ulcer disease to examine their differential effects on signaling pathways and IL-8 gene response in gastric epithelial cells. IL-8 mRNA level is elevated in response to high (100) multiplicity of infection (MOI) independent of cagA, vacA, and dupA gene characteristics. By lower MOIs (1 or 10), only cagA + strains significantly induce IL-8 gene expression. This is based on differential regulation of IL-8 promoter activity. Analysis of intracellular signaling pathways indicates that H. pylori clinical isolates induce IL-8 gene transcription through NF-κB p65, but by a MOI-dependent differential activation of MAPK pathways. Thus, the major virulence factors of H. pylori CagA, VacA, and DupA might play a minor role in the level of IL-8 gene response to a high bacterial load.

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Acknowledgments

This work was supported by grants from Deutsche Forschungsgemeinschaft SFB 566 and European research council IOF.

We thank Meredith Millis and Kimberly Yeatts for critically reading the manuscript.

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Authors and Affiliations

  1. Institute of Pharmacology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany

    Birgit Ritter, Petra Kilian, Klaus Resch & Winfried Beil

  2. Department of Chemical Biology, Helmholtz Centre for Infection Research, Inhoffenstraβe 7, 38124, Braunschweig, Germany

    Marc Rene Reboll, Ronald Frank & Mahtab Nourbakhsh

  3. Diabetes, Cardiovascular and Metabolic Diseases Division, Translational Genomics Research Institute, 445 North Fifth Street, Phoenix, AZ, 85004, USA

    Johanna Kay DiStefano

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  1. Birgit Ritter
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Correspondence to Mahtab Nourbakhsh.

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Ritter, B., Kilian, P., Reboll, M.R. et al. Differential Effects of Multiplicity of Infection on Helicobacter pylori-Induced Signaling Pathways and Interleukin-8 Gene Transcription. J Clin Immunol 31, 60–68 (2011). https://doi.org/10.1007/s10875-010-9467-5

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  • DOI: https://doi.org/10.1007/s10875-010-9467-5

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