Molecular basis for up-regulation by inflammatory cytokines of Shiga toxin 1 cytotoxicity and globotriaosylceramide expression.
Publication/Presentation Date
10-1-2002
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.
Volume
186
Issue
7
First Page
976
Last Page
982
ISSN
0022-1899
Published In/Presented At
Stricklett, P. K., Hughes, A. K., Ergonul, Z., & Kohan, D. E. (2002). Molecular basis for up-regulation by inflammatory cytokines of Shiga toxin 1 cytotoxicity and globotriaosylceramide expression. The Journal of infectious diseases, 186(7), 976–982. https://doi.org/10.1086/344053
Disciplines
Medicine and Health Sciences | Pediatrics
PubMedID
12232838
Department(s)
Department of Pediatrics
Document Type
Article