Class II MHC molecules on gastric epithelial cells act as receptors for Helicobacter pylori urease and signal apoptosis of the epithelium

X. J. Fan, H. Gunasena, M. Gonzales, R. Almanza, Z. Cheng, G. Ye, C. Barrera, S. E. Crowe, P. B. Ernst, Victor Reyes

Research output: Contribution to journalArticle

Abstract

Helicobacter pylori (Hp) damages the gastric epithelium and may lead to peptic ulcer and cancer. We have shown that Hp binds to class IIMHC on gastric epithelial cells and signals apoptosis. However, the Hp proteins that bind to class II MHC and trigger apoptosis are not known. Since urease is a major Hp product that stimulates cytokine secretion by class II MHC+ cells, we hypothesized that apoptosis in gastric epithelial cells is signaled through class II MHC molecules subsequent to urease binding. To determine the interaction of urease with class II MHC, urease-coated beads were incubated with [35S] labeled proteins from gastric epithelial cell lines (Kato III, N87 and AGS) as well as HLA-DR1-transfected (1D12) COS-1 cells. Bound proteins were eluted and electrophoresis analysis revealed class II MHC among the eluted proteins. IFN-γ increased the binding of urease to Kato III and N87, which are class II MHC-, but not to AGS, which is class IIMHC. Urease binding was blocked by anti-class MHC mAb. Also, urease bound only to HLA-DR1-transfected COS-1 (1D12) cells but not to COS-1 cells. To confirm the interaction of urease with class II MHC, 96-well plates were coated with urease, to which binding affinity-purified class II MHC from [35S] labeled gastric epithelial cells were added. Gel electrophoresis of the bound material confirmed that class II MHC α and β chains bound to the wells coated with urease but not to the control wells. Urease induced apoptosis in class II MHC-, but not in class II MHC- cell lines as determined by ELISA and this apoptosis was blocked by Fab fragments from anti-class II MHC. These observations uncover a new role for H. pylori urease in associated diseases as well as a novel ligand for class II MHC.

Original languageEnglish (US)
JournalFASEB Journal
Volume12
Issue number5
StatePublished - Mar 20 1998

Fingerprint

Urease
Helicobacter pylori
urease
Stomach
stomach
epithelial cells
epithelium
Epithelium
apoptosis
Epithelial Cells
Apoptosis
receptors
Molecules
COS Cells
HLA-DR1 Antigen
Electrophoresis
Proteins
proteins
cell lines
cells

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

Cite this

Class II MHC molecules on gastric epithelial cells act as receptors for Helicobacter pylori urease and signal apoptosis of the epithelium. / Fan, X. J.; Gunasena, H.; Gonzales, M.; Almanza, R.; Cheng, Z.; Ye, G.; Barrera, C.; Crowe, S. E.; Ernst, P. B.; Reyes, Victor.

In: FASEB Journal, Vol. 12, No. 5, 20.03.1998.

Research output: Contribution to journalArticle

Fan, XJ, Gunasena, H, Gonzales, M, Almanza, R, Cheng, Z, Ye, G, Barrera, C, Crowe, SE, Ernst, PB & Reyes, V 1998, 'Class II MHC molecules on gastric epithelial cells act as receptors for Helicobacter pylori urease and signal apoptosis of the epithelium', FASEB Journal, vol. 12, no. 5.
Fan, X. J. ; Gunasena, H. ; Gonzales, M. ; Almanza, R. ; Cheng, Z. ; Ye, G. ; Barrera, C. ; Crowe, S. E. ; Ernst, P. B. ; Reyes, Victor. / Class II MHC molecules on gastric epithelial cells act as receptors for Helicobacter pylori urease and signal apoptosis of the epithelium. In: FASEB Journal. 1998 ; Vol. 12, No. 5.
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AU - Reyes, Victor

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