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

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

Research output: Contribution to journalArticle

1 Citation (Scopus)

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 proapoptotic 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.

Original languageEnglish (US)
Pages (from-to)5306-5310
Number of pages5
JournalWorld Journal of Gastroenterology
Volume12
Issue number33
StatePublished - Sep 7 2006

Fingerprint

Pylorus
Stomach
Caspases
Epithelial Cells
Apoptosis
Ligation
Immunoglobulin M
Infection
CD95 Antigens
Antibodies
Confocal Microscopy
Caspase 3
Cytokines
Bacteria
Cell Line
Research

Keywords

  • Apoptosis
  • Gastric epithelial cell
  • H pylori
  • MHC class II

ASJC Scopus subject areas

  • Gastroenterology

Cite this

H pylori receptor MHC class II contributes to the dynamic gastric epithelial apoptic response. / Bland, David A.; Suarez, Giovanni; Beswick, Ellen J.; Sierra, Johanna C.; Reyes, Victor.

In: World Journal of Gastroenterology, Vol. 12, No. 33, 07.09.2006, p. 5306-5310.

Research output: Contribution to journalArticle

Bland, David A. ; Suarez, Giovanni ; Beswick, Ellen J. ; Sierra, Johanna C. ; Reyes, Victor. / H pylori receptor MHC class II contributes to the dynamic gastric epithelial apoptic response. In: World Journal of Gastroenterology. 2006 ; Vol. 12, No. 33. pp. 5306-5310.
@article{6b24fb891f784add848b466f4ffe8108,
title = "H pylori receptor MHC class II contributes to the dynamic gastric epithelial apoptic response",
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 proapoptotic 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 = "Apoptosis, Gastric epithelial cell, H pylori, MHC class II",
author = "Bland, {David A.} and Giovanni Suarez and Beswick, {Ellen J.} and Sierra, {Johanna C.} and Victor Reyes",
year = "2006",
month = "9",
day = "7",
language = "English (US)",
volume = "12",
pages = "5306--5310",
journal = "World Journal of Gastroenterology",
issn = "1007-9327",
publisher = "WJG Press",
number = "33",

}

TY - JOUR

T1 - H pylori receptor MHC class II contributes to the dynamic gastric epithelial apoptic response

AU - Bland, David A.

AU - Suarez, Giovanni

AU - Beswick, Ellen J.

AU - Sierra, Johanna C.

AU - Reyes, Victor

PY - 2006/9/7

Y1 - 2006/9/7

N2 - 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 proapoptotic 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.

AB - 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 proapoptotic 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.

KW - Apoptosis

KW - Gastric epithelial cell

KW - H pylori

KW - MHC class II

UR - http://www.scopus.com/inward/record.url?scp=33749406348&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33749406348&partnerID=8YFLogxK

M3 - Article

C2 - 16981259

AN - SCOPUS:33749406348

VL - 12

SP - 5306

EP - 5310

JO - World Journal of Gastroenterology

JF - World Journal of Gastroenterology

SN - 1007-9327

IS - 33

ER -