TPA AND BUTYRATE INCREASE CELL SENSITIVITY TO THE VACUOLATING TOXIN OF HELICOBACTER-PYLORI

The Helicobacter pylori toxin VacA induces large membrane-bound vacuol ar compartments of late endosomal/lysosomal origin, Pre-treatment of c ells with TPA and butyrate enhances the toxin induced vacuolisation up to 20 times, depending on the cell line, whereas other differentiatin g factors such as DMSO, EGF, valeric and retinoic acid have no effect. The higher toxin sensitivity induced by TPA does not result from an i ncreased surface binding or endocytosis, The effect of TPA is apparent after several hours from addition and is inhibited by a PKC specific inhibitor. These data suggest that expression of cellular proteins, ot her than the toxin receptor(s), influences the vacuolating activity of VacA and mag contribute to the sensitivity of different cell lines. T he present findings define the most sensitive in vitro assay of the ac tivity of VacA, (C) 1998 Federation of European Biochemical Societies.