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

Verocytotoxin 1 and 2 (VT1 and 2) produced by verocytotoxin-producing Escherichia coli have been considered to play an important role in the pathogenesis of glomerular and tubular damage in the epidemic form of hemolytic uremic syndrome (HUS). VTs are known to be cytotoxic to culture cells by inhibiting cellular protein synthesis. In this in vitro study, the mechanism(s) of tubular damage in HUS and the ability of VT1 to induce apoptosis in normal human renal proximal tubular epithelial cells (HRPTEC) were examined. VT1 markedly reduced cell viability of HRPTEC and rapidly inhibited overall protein synthesis. VT1 directly induced apoptotic cell death in HRPTEC in a dose- and time-dependent fashion, and co-incubation with tumor necrosis factor-α enhanced the VT1-induced apoptosis. These results suggest that apoptosis induced by VT1, possibly in concert with host cytokines, in renal tubular cells may contribute to the tubular damage in HUS. Received: 15 December 1998