Induction of apoptosis in human renal proximal tubular epithelial cells byEscherichia coli verocytotoxin 1 in vitro

Verocytotoxin 1 and 2 (VT1 and 2) produced by verocytotoxin-producing Esche richia coli have been considered to play an important role in the pathogene sis of glomerular and tubular damage in the epidemic form of hemolytic urem ic syndrome (HUS). VTs are known to be cytotoxic to culture cells by inhibi ting cellular protein synthesis. In this in vitro study, the mechanism(s) o f tubular damage in HUS and the ability of VT1 to induce apoptosis in norma l human renal proximal tubular epithelial cells (HRPTEC) were examined. VT1 markedly reduced cell viability of HRPTEC and rapidly inhibited overall pr otein synthesis. VT1 directly induced apoptotic cell death in HRPTEC in a d ose- and time-dependent fashion, and co-incubation with tumor necrosis fact or-a enhanced the VT1-induced apoptosis. These results suggest that apoptos is induced by VT1, possibly in concert with host cytokines, in renal tubula r cells may contribute to the tubular damage in HUS.