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

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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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Acknowledgement

A grant from the Dutch Kidney Foundation supported this investigation: grant 97.1645.

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Authors and Affiliations

  1. Department of Pediatrics, University Hospital Nijmegen, Nijmegen, The Netherlands

    D. Maroeska te Loo, Leo Monnens, Thea van der Velden & Lambertus van den Heuvel

  2. Laboratory for Foodborne Zoonoses Population and Public Health Branch, Health Canada, Guelph, ON, Canada

    Mohammed Karmali

  3. Institute for Cardiovascular Research, Vrije Universiteit, Amsterdam, The Netherlands

    Victor van Hinsbergh

  4. Department of Pediatrics, University Medical Center Nijmegen, 6500 HB, Nijmegen, The Netherlands

    D. Maroeska te Loo

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  1. D. Maroeska te Loo
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  2. Leo Monnens
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  3. Thea van der Velden
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  4. Mohammed Karmali
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  5. Lambertus van den Heuvel
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  6. Victor van Hinsbergh
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Correspondence to D. Maroeska te Loo.

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te Loo, D.M., Monnens, L., van der Velden, T. et al. Shiga toxin-1 affects nitric oxide production by human glomerular endothelial and mesangial cells. Pediatr Nephrol 21, 1815–1823 (2006). https://doi.org/10.1007/s00467-006-0232-1

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  • DOI: https://doi.org/10.1007/s00467-006-0232-1

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