H pylori receptor MHC class II contributes to the dynamic gastric epithelial apoptotic response

David A. Bland, Giovanni Suarez, Ellen J. Beswick, Johanna C. Sierra, Victor E. Reyes

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

Aim: To investigate the role of MHC class II in the modulation of gastric epithelial cell apoptosis induced by H pylori infection. Methods: After stimulating a human gastric epithelial cell line with bacteria or agonist antibodies specific for MHC class II and CD95, the quantitation of apoptotic and anti-apoptotic events, including caspase activation, BCL-2 activation, and FADD recruitment, was performed with a fluorometric assay, a cytometric bead array, and confocal microscopy, respectively. Results: Pretreatment of N87 cells with the anti-MHC class II IgM antibody RFD1 resulted in a reduction in global caspase activation at 24 h of H pylori infection. When caspase 3 activation was specifically measured, crosslinking of MHC class II resulted in markedly reduced caspase activation, while simple ligation of MHC class II did not. Crosslinking of MHC class II also resulted in an increased activation of the anti-apoptosis molecule BCL-2 compared to simple ligation. Confocal microscope analysis demonstrated that the pretreatment of gastric epithelial cells with a crosslinking anti-MHC class II IgM blocked the recruitment of FADD to the cell surface. Conclusion: The ability of MHC class II to modulate gastric epithelial apoptosis is at least partially dependent on its crosslinking. The crosslinking of this molecule has anti-apoptotic effects during the earlier time points of H pylori infection. This effect is possibly mediated by the ability of MHC class II to modulate the activation of the pro-apoptotic receptor Fas by blocking the recruitment of the accessory molecule FADD, and this delay in apoptosis induction could allow for prolonged cytokine secretion by H pylori infected gastric epithelial cells.

Original languageEnglish (US)
Pages (from-to)4689-4693
Number of pages5
JournalWorld journal of gastroenterology
Volume12
Issue number29
DOIs
StatePublished - Aug 7 2006

Keywords

  • Apoptosis
  • Class II MHC
  • Epithelium
  • H pylori

ASJC Scopus subject areas

  • Gastroenterology

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