Ruth Veach
Last active: 4/25/2016

Suppression of Staphylococcal Enterotoxin B-induced Toxicity by a Nuclear Import Inhibitor.

Liu D, Liu XY, Robinson D, Burnett C, Jackson C, Seele L, Veach RA, Downs S, Collins RD, Ballard DW, Hawiger J
J Biol Chem. 2004 279 (18): 19239-46

PMID: 14732709 · DOI:10.1074/jbc.M313442200

Staphylococcal enterotoxin B and related toxins that target T cells have the capacity to elicit systemic inflammation, tissue injury, and death. Genes that encode mediators of inflammation can be globally inhibited by blocking the nuclear import of stress-responsive transcription factors. Here we show that cell-permeant peptides targeting Rch1/importin alpha/karyopherin alpha 2, a nuclear import adaptor protein, are delivered to T cells where they inhibit the staphylococcal enterotoxin B-induced production of inflammatory cytokines ex vivo in cultured primary spleen cells and in vivo. The systemic production of tumor necrosis factor alpha, interferon gamma, and interleukin-6 was attenuated in mice either by a cell-permeant cyclized form of SN50 peptide or by a transgene whose product suppresses the nuclear import of transcription factor nuclear factor kappa B in T cells. The extent of liver apoptosis and hemorrhagic necrosis was also reduced, which correlated with significantly decreased mortality rates. These findings highlight nuclear import inhibitors as a potentially useful countermeasure for staphylococcal enterotoxin B and other toxins that trigger harmful systemic inflammatory responses.

MeSH Terms (14)

Active Transport, Cell Nucleus Adaptor Proteins, Vesicular Transport alpha Karyopherins Amino Acid Sequence Animals Cell Death Cell Membrane Permeability Cytokines Enterotoxins Liver Mice NF-kappa B Peptides T-Lymphocytes

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