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• W2053399894 endingPage "1737" @default.
• W2053399894 startingPage "1737" @default.
• W2053399894 abstract "The B subunit of Escherichia coli heat-labile enterotoxin (EtxB) is a potent immunomodulatory molecule capable of treating and preventing autoimmune disease. These properties result from its ability to bind to glycolipid receptors, principally GM1 ganglioside, and modulate immune cell function. EtxB receptor binding causes B cell activation, modulates monocyte cytokine secretion and triggers apoptosis of CD8+ T cells. These wide-ranging effects suggest that B subunit receptor interaction triggers signaling events affecting cellular differentiation. We have investigated the processes by which EtxB induces CD8+ T cell apoptosis. We show that receptor interaction by EtxB activates caspase-3 in CD8+ but not in CD4+ T cells. Inhibition of caspase-3 blocks the apoptotic process. EtxB induces the activation of NF-κB in both CD8+ and CD4+ T cells. The findings that (i) SN50, a peptide inhibitor of NF-κB nuclear translocation, prevents caspase-3 activation and subsequent apoptosis, and (ii) CD8+CD4– thymocytes from transgenic mice expressing a dominant-negative form of the IκBα protein were markedly less susceptible to EtxB-induced apoptosis than cells from wild-type mice, indicate that NF-κB is important in the induction of the apoptotic pathway. Further investigations revealed that while caspase-8 activity is detected concomitant to caspase-3, caspase-9 activation, following mitochondrial cytochrome c release, is detectable later on. These observations are consistent with death receptor-mediated signaling, however, experiments using lpr/lpr and p55 TNFR –/– mice rule out the involvement of Fas and the p55 TNF receptor, respectively. The data therefore indicate that EtxB-mediated apoptosis occurs via a novel pathway involving NF-κB." @default.
• W2053399894 created "2016-06-24" @default.
• W2053399894 creator A5008014053 @default.
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• W2053399894 date "2002-06-01" @default.
• W2053399894 modified "2023-10-17" @default.
• W2053399894 title "CD8+ T cell apoptosis induced by Escherichia coli heat-labile enterotoxin B subunit occurs via a novel pathway involving NF-κB-dependent caspase activation" @default.
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• W2053399894 doi "https://doi.org/10.1002/1521-4141(200206)32:6<1737::aid-immu1737>3.0.co;2-j" @default.
• W2053399894 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/12115657" @default.
• W2053399894 hasPublicationYear "2002" @default.
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