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• W2159442887 endingPage "1121" @default.
• W2159442887 startingPage "1115" @default.
• W2159442887 abstract "ABSTRACT Escherichia coli O157:H7 Shiga toxin 2 (Stx2), one of the causative agents of hemolytic-uremic syndrome, is toxic to endothelial cells, including primary cultured human umbilical vein endothelial cells (HUVEC). This sensitivity of cells to Stx2 can be increased with either lipopolysaccharide (LPS) or tumor necrosis factor alpha (TNF-α). The goal of the present study was to identify the intracellular signaling pathway(s) by which LPS and TNF-α sensitize HUVEC to the cytotoxic effects of Stx2. To identify these pathways, specific pharmacological inhibitors and small interfering RNAs were tested with cell viability endpoints. A time course and dose response experiment for HUVEC exposure to LPS and TNF-α showed that a relatively short exposure to either agonist was sufficient to sensitize the cells to Stx2 and that both agonists stimulated intracellular signaling pathways within a short time. Cell viability assays indicated that the p38 mitogen-activated protein kinase (MAPK) inhibitors SB202190 and SB203580 and the general protein synthesis inhibitor cycloheximide inhibited both the LPS and TNF-α sensitization of HUVEC to Stx2, while all other inhibitors tested did not inhibit this sensitization. Additionally, SB202190 reduced the cellular globotriaosylceramide content under LPS- and TNF-α-induced conditions. In conclusion, our results show that LPS and TNF-α induction of Stx2 sensitivity in HUVEC is mediated through a pathway that includes p38 MAPK. These results indicate that inhibition of p38 MAPK in endothelial cells may protect a host from the deleterious effects of Stx2." @default.
• W2159442887 created "2016-06-24" @default.
• W2159442887 creator A5009037552 @default.
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• W2159442887 creator A5058436904 @default.
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• W2159442887 date "2008-03-01" @default.
• W2159442887 modified "2023-09-26" @default.
• W2159442887 title "p38 Mitogen-Activated Protein Kinase Mediates Lipopolysaccharide and Tumor Necrosis Factor Alpha Induction of Shiga Toxin 2 Sensitivity in Human Umbilical Vein Endothelial Cells" @default.
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• W2159442887 doi "https://doi.org/10.1128/iai.01300-07" @default.
• W2159442887 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2258847" @default.
• W2159442887 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/18086809" @default.
• W2159442887 hasPublicationYear "2008" @default.
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