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 been felt to be the primary renal target of Stx-1; however, recent studies suggest that renal epithelial cells may also be responsive. To further examine this issue, we evaluated the responsiveness of human glomerular epithelial 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 serum 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 necrosis factor-alpha (TNF-alpha), and butyrate increased Stx-1 cytotoxicity and total cell Gb3 levels. These agents, with the exception of TNF-alpha, also increased Stx-1 binding to GECs. IL-6 failed to alter Stx-1 toxicity, binding, or Gb3 content.


CONCLUSIONS
These studies indicate that GECs are sensitive to the cytotoxic effects of Stx-1 and that inflammatory factors can increase toxin responsiveness. GECs may be a target of Stx-1 action in Stx HUS.
Hughes
A K
AK
University of Utah School of Medicine and Salt Lake Veterans Affairs Medical Center, Salt Lake City, Utah 84132, USA.
Stricklett
P K
PK
Schmid
D
D
Kohan
D E
DE
D001427:Bacterial Toxins / Q000494:pharmacology*; D002087:Butyrates / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D004357:Drug Synergism; D004847:Epithelial Cells / Q000187:drug effects; D006801:Humans; D018836:Inflammation Mediators / Q000494:pharmacology; D007678:Kidney Glomerulus / Q000166:cytology / Q000187:drug effects*; D008070:Lipopolysaccharides / Q000494:pharmacology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology*; D022603:Shiga Toxins
D001427:Bacterial Toxins; D002087:Butyrates; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D011500:Protein Synthesis Inhibitors; D022603:Shiga Toxins; D003513:Cycloheximide