The Helicobacter pylori urease B subunit binds to CD74 on gastric epithelial cells and induces NF-κB activation and interleukin-8 production

Ellen J. Beswick, Iryna Pinchuk, Kyle Minch, Giovanni Suarez, Johanna C. Sierra, Yoshio Yamaoka, Victor Reyes

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

The pathogenesis associated with Helicobacter pylori infection is the result of both bacterial factors and the host response. We have previously shown that H. pylori binds to CD74 on gastric epithelial cells. In this study, we sought to identify the bacterial protein responsible for this interaction. H. pylori urease from a pool of bacterial surface proteins was found to coprecipitate with CD74. To determine how urease binds to CD74, we used recombinant urease A and B subunits. Recombinant urease B was found to bind directly to CD74 in immunoprecipitation and flow cytometry studies. By utilizing both recombinant urease subunits and urease B knockout bacteria, the urease B-CD74 interaction was shown to induce NF-κB activation and interleukin-8 (IL-8) production. This response was decreased by blocking CD74 with monoclonal antibodies. Further confirmation of the interaction of urease B with CD74 was obtained using a fibroblast cell line transfected with CD74 that also responded with NF-κB activation and IL-8 production. The binding of the H. pylori urease B subunit to CD74 expressed on gastric epithelial cells presents a novel insight into a previously unrecognized H. pylori interaction that may contribute to the proinflammatory immune response seen during infection.

Original languageEnglish (US)
Pages (from-to)1148-1155
Number of pages8
JournalInfection and Immunity
Volume74
Issue number2
DOIs
StatePublished - Feb 2006

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Urease
Interleukin-8
Helicobacter pylori
Stomach
Epithelial Cells
Bacterial Proteins
Helicobacter Infections
Immunoprecipitation
Flow Cytometry
Membrane Proteins
Fibroblasts
Monoclonal Antibodies
Bacteria
Cell Line

ASJC Scopus subject areas

  • Immunology

Cite this

The Helicobacter pylori urease B subunit binds to CD74 on gastric epithelial cells and induces NF-κB activation and interleukin-8 production. / Beswick, Ellen J.; Pinchuk, Iryna; Minch, Kyle; Suarez, Giovanni; Sierra, Johanna C.; Yamaoka, Yoshio; Reyes, Victor.

In: Infection and Immunity, Vol. 74, No. 2, 02.2006, p. 1148-1155.

Research output: Contribution to journalArticle

Beswick, Ellen J. ; Pinchuk, Iryna ; Minch, Kyle ; Suarez, Giovanni ; Sierra, Johanna C. ; Yamaoka, Yoshio ; Reyes, Victor. / The Helicobacter pylori urease B subunit binds to CD74 on gastric epithelial cells and induces NF-κB activation and interleukin-8 production. In: Infection and Immunity. 2006 ; Vol. 74, No. 2. pp. 1148-1155.
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