Molecular Basis for Up-Regulation by Inflammatory Cytokines of Shiga Toxin 1 Cytotoxicity and Globotriaosylceramide Expression.
In: Journal of Infectious Diseases, Jg. 186 (2002-10-01), Heft 7, S. 976-982
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Zugriff:
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 α-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 α-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. [ABSTRACT FROM AUTHOR]
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Titel: |
Molecular Basis for Up-Regulation by Inflammatory Cytokines of Shiga Toxin 1 Cytotoxicity and Globotriaosylceramide Expression.
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Autor/in / Beteiligte Person: | Stricklett, Peter G. ; Hughes, Alisa K. ; Ergonul, Zuhal ; Kohan, Donald E. |
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Zeitschrift: | Journal of Infectious Diseases, Jg. 186 (2002-10-01), Heft 7, S. 976-982 |
Veröffentlichung: | 2002 |
Medientyp: | academicJournal |
ISSN: | 0022-1899 (print) |
DOI: | 10.1086/344053 |
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