title: H pylori receptor MHC class II contributes to the dynamic gastric epithelial apoptotic response.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pediatrics, GI Immunology Core, Texas Gulf Coast Digestive Diseases Center, Technical Director, Child Health Research Center, The University of Texas Medical Branch at Galveston, Galveston, TX 77555-0366, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Bland
authors.forename: Giovanni
authors.initials: G
authors.lastname: Suarez
authors.forename: Ellen J
authors.initials: EJ
authors.lastname: Beswick
authors.forename: Johanna C
authors.initials: JC
authors.lastname: Sierra
authors.forename: Victor E
authors.initials: VE
authors.lastname: Reyes
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000502:physiology; D000906:Antibodies / Q000276:immunology / Q000494:pharmacology; D017209:Apoptosis / Q000502:physiology*; D053148:Caspase 3; D020169:Caspases / Q000502:physiology; D002460:Cell Line; D004789:Enzyme Activation / Q000502:physiology; D004847:Epithelial Cells / Q000187:drug effects / Q000382:microbiology / Q000473:pathology; D053200:Fas-Associated Death Domain Protein; D016481:Helicobacter Infections / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*; D016480:Helicobacter pylori / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology / Q000502:physiology*; D006801:Humans; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000502:physiology; D013270:Stomach / Q000187:drug effects / Q000382:microbiology* / Q000473:pathology* / Q000503:physiopathology; D019014:fas Receptor / Q000276:immunology / Q000502:physiology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000906:Antibodies; C505533:FADD protein, human; D053200:Fas-Associated Death Domain Protein; D000949:Histocompatibility Antigens Class II; D019253:Proto-Oncogene Proteins c-bcl-2; D019014:fas Receptor; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases