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Helicobacter pylori Water Extract Induces Interleukin-8 Production by Gastric Epithelial Cells

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Abstract

In Helicobacter pylori-associated gastricmucosal injury, interleukin (IL)-8, a potent leukocytechemoattractant, is produced by epithelial cellsinfected by H. pylori and directs neutrophils to thegastric mucosa. According to previous studies, the IL-8production requires direct contact between the bacteriaand epithelial cells. The aims of the present study wereto determine whether an H. pylori water extract (HPE) induces IL-8 production by gastricepithelial cells and to characterize IL-8-inducingsubstances in HPE. Extracts were prepared from astandard strain and from strains obtained from patientswith gastric ulcers. After addition of HPE to MKN 45cells, a gastric cancer cell line, IL-8 in supernatantsand IL-8 mRNA were measured by immunoassay and reversetranscription-polymerase chain reaction, respectively. For characterization, active fractions obtainedby gel filtration of standard-strain HPE were treated byheating or trypsinization. To study the signal pathwayleading to IL-8 production, inhibitors for protein kinase A (PKA), protein kinase C (PKC),or protein tyrosine kinase (PTK) were incubated withMKN45 cells before HPE stimulation. HPE from thestandard strain and one of these clinical strainsinduced IL-8 production. Lipopolysaccharide or cagA inthe strains showed no correlation with IL-8concentration. Standard-strain HPE induced IL-8 mRNAexpression in MKN 45 cells. Gel filtration localizedactivity to a low-molecular-weight fraction of about 7kDa, which was resistant to heat and trypsin digestion.PKC inhibitors significantly blocked HPE-induced IL-8production by MKN 45 cells; however, the PKA inhibitor or PTK inhibitors showed a partial inhibitoryeffect. HPE contains a nonprotein substance of lowmolecular weight that is responsible for IL-8 inductionin gastric epithelial cells. This induction is mainly dependent on the activation of PKC butpartially also dependent on PKA or PTK.

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Authors
  1. Kyoichi Kassai
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  2. Toshikazu Yoshikawa
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  3. Norimasa Yoshida
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  4. Akira Hashiramoto
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  5. Motoharu Kondo
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  6. Hironobu Murase
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Kassai, K., Yoshikawa, T., Yoshida, N. et al. Helicobacter pylori Water Extract Induces Interleukin-8 Production by Gastric Epithelial Cells. Dig Dis Sci 44, 237–242 (1999). https://doi.org/10.1023/A:1026629812245

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  • DOI: https://doi.org/10.1023/A:1026629812245

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