Molecular basis for up-regulation by inflammatory cytokines of Shiga toxin 1 cytotoxicity and globotriaosylceramide expression. Academic Article uri icon

Overview

abstract

  • Mortality in postdiarrheal hemolytic-uremic syndrome (HUS) is associated with brain injury. Normally, brain cells are resistant to Shiga toxin (Stx), the putative pathogenic toxin in HUS. However, exposure of human brain endothelial cells (HBECs) to tumor necrosis factor (TNF) and/or interleukin (IL)-1 markedly up-regulates Stx receptor (globotriaosylceramide; Gb3) expression and cytotoxicity. To investigate how Gb3 is augmented, ceramide glucosyltransferase (CGT), lactosylceramide synthase (GalT2), Gb3 synthase (GalT6), and alpha-galactosidase were studied in HBECs exposed to TNF and IL-1. TNF, both alone and in combination with IL-1, increased Stx-1 toxicity, Gb3 content, and Stx-1 binding. TNF in combination with IL-1 increased CGT, GalT2, and GalT6 but did not change alpha-galactosidase activities or mRNA levels. Cytokine treatment did not change CGT, GalT2, or GalT6 mRNA half-lives. Thus, inflammatory cytokine up-regulation of the sensitivity of HBECs to Stx-1 is the result of up-regulation, most likely via transcription, of the activities of 3 enzymes involved in Gb3 synthesis.

publication date

  • September 13, 2002

Research

keywords

  • Cytokines
  • Shiga Toxin 1
  • Trihexosylceramides

Identity

Scopus Document Identifier

  • 0036785397

Digital Object Identifier (DOI)

  • 10.1086/344053

PubMed ID

  • 12232838

Additional Document Info

volume

  • 186

issue

  • 7