The Helicobacter pylori urease B subunit binds to CD74 on gastric epithelial cells and induces NF-kappaB activation and interleukin-8 production.
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-kappaB 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-kappaB 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.
Beswick
Ellen J
EJ
Department of Pediatrics, Children's Hospital, Room 2.300, University of Texas Medical Branch, 301 University Blvd., Galveston, TX 77555, USA.
Pinchuk
Irina V
IV
Minch
Kyle
K
Suarez
Giovanni
G
Sierra
Johanna C
JC
Yamaoka
Yoshio
Y
Reyes
Victor E
VE
D000944:Antigens, Differentiation, B-Lymphocyte / Q000378:metabolism*; D002460:Cell Line; D004847:Epithelial Cells / Q000378:metabolism / Q000382:microbiology; D005347:Fibroblasts / Q000382:microbiology; D005753:Gastric Mucosa / Q000166:cytology / Q000378:metabolism / Q000382:microbiology; D016480:Helicobacter pylori / Q000201:enzymology* / Q000235:genetics / Q000472:pathogenicity*; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation; D014510:Urease / Q000235:genetics / Q000378:metabolism*
D000944:Antigens, Differentiation, B-Lymphocyte; D000949:Histocompatibility Antigens Class II; D016209:Interleukin-8; D016328:NF-kappa B; D011994:Recombinant Proteins; C045084:invariant chain; D014510:Urease