H Pylori
Copyright ©2006 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Sep 7, 2006; 12(33): 5306-5310
Published online Sep 7, 2006. doi: 10.3748/wjg.v12.i33.5306
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
David A Bland, Victor E Reyes, Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, United States
Giovanni Suarez, Ellen J Beswick, Johanna C Sierra, Victor E Reyes, Department of Pediatrics, University of Texas Medical Branch, Galveston, Texas, United States
Supported by the National Institutes of Health Grants DK50669, DK56338 and National Institutes of Health T32 AI007536-06 Training Grant
Correspondence to: Dr. Victor E Reyes, Children’s Hospital, Room 2.300, University of Texas Medical Branch, 301 University Blvd. Galveston, TX 77555, United States. vreyes@utmb.edu
Telephone: +1-409-7721761 Fax: +1-409-7721761
Received: May 10, 2005
Revised: May 28, 2005
Accepted: June 9, 2005
Published online: September 7, 2006
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 a marked 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 results presented here demonstrate that the ability of MHC class II to modulate gastric epithelial apoptosis is at least partially dependent on its crosslinking. Furthermore, while previous research has demonstrated that MHC class II signaling can be pro-apoptotic during extended ligation, we have shown that 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.

Keywords: H pylori, MHC class II, Gastric epithelial cell, Apoptosis