Cytotoxic effect of Shiga toxin-1 on human glomerular epithelial cells

Background Shiga toxin-1 (Stx-1) has been implicated in the pathogenesis of postdiarrheal hemolytic-uremic syndrome (Stx HUS). Endothelial cells had b een felt to be the primary renal target of Stx-1; however, recent studies s uggest that renal epithelial cells may also be responsive. To further exami ne this issue, we evaluated the responsiveness of human glomerular epitheli al cells (GECs) to the cytotoxic effects of Stx-1. Methods. Cultured GECs were exposed to Stx-1 in the presence and absence of a variety of inflammatory factors likely to be elevated in the kidney or s erum of patients with Stx HUS. Cell survival, protein synthesis, total cell Gb3 levels and synthesis, and Stx-1 binding were measured. Results. GECs were sensitive to Stx-1, with an LD50 of approximately 10(-7) g/L (1.4 pmol/L). Interleukin-1 (IL-1), lipopolysaccharide (LPS), tumor ne crosis factor-alpha (TNF-alpha), and butyrate increased Stx-1 cytotoxicity and total cell Gb3 levels. These agents, with the exception of TNF-alpha, a lso increased Stx-1 binding to GECs. IL-6 failed to alter Stx-1 toxicity, b inding, or Gb3 content. Conclusions. These studies indicate that GECs are sensitive to the cytotoxi c effects of Stx-1 and that inflammatory factors can increase toxin respons iveness. GECs may be a target of Stx-1 action in Stx HUS.