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01.12.2006 | Original Article

Shiga toxin-1 affects nitric oxide production by human glomerular endothelial and mesangial cells

verfasst von: D. Maroeska te Loo, Leo Monnens, Thea van der Velden, Mohammed Karmali, Lambertus van den Heuvel, Victor van Hinsbergh

Erschienen in: Pediatric Nephrology | Ausgabe 12/2006

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Abstract

Acute renal failure hallmarks the pathogenesis of the epidemic form of hemolytic uremic syndrome (D+HUS), which is caused by E. coli strains that produce Shiga-like toxin (Stx). In this study, we investigated the influence of Stx-1 on nitric oxide (NO) production by human glomerular microvascular endothelial cells (GMVEC) and human mesangial cells. NO synthesis by human mesangial cells is in the micromolar range and that of GMVEC in the picomolar range. Stx-1 reduced NO production in non-stimulated GMVEC (5 nmol/l Stx-1 required) without inhibition of protein synthesis. In non-stimulated and TNFα-pretreated mesangial cells, NO production was reduced with a maximal reduction at 10 fmol/l shiga toxin. The cellular iNOS antigen content in mesangial cells was reduced in a concentration-dependent way (10 fmol/l-100 pmol/l), while partial inhibition of protein synthesis required 10 nmol/l Stx-1 in these cells. Our in vitro data suggest that Stx may reduce NO synthesis during the course of HUS development, contributing to the aggravation of the thrombotic microangiopathy and renal failure as observed in HUS.

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Titel: Shiga toxin-1 affects nitric oxide production by human glomerular endothelial and mesangial cells
verfasst von: D. Maroeska te Loo
Leo Monnens
Thea van der Velden
Mohammed Karmali
Lambertus van den Heuvel
Victor van Hinsbergh
Publikationsdatum: 01.12.2006
Verlag: Springer Berlin Heidelberg
Erschienen in: Pediatric Nephrology / Ausgabe 12/2006
Print ISSN: 0931-041X
Elektronische ISSN: 1432-198X
DOI: https://doi.org/10.1007/s00467-006-0232-1

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