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Shiga toxin 1‐induced activation of c‐Jun NH 2 ‐terminal kinase and p38 in the human monocytic cell line THP‐1: possible involvement in the production of TNF‐α
Author(s) -
Foster Gregory H.,
Tesh Ver L.
Publication year - 2002
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.71.1.107
Subject(s) - proinflammatory cytokine , biology , tumor necrosis factor alpha , thp1 cell line , p38 mitogen activated protein kinases , shiga toxin , cytokine , microbiology and biotechnology , toxin , immunology , kinase , cell culture , protein kinase a , inflammation , biochemistry , escherichia coli , genetics , gene
Shiga toxin‐producing enterohemorrhagic E. coli infections cause bloody diarrhea, which may progress to life‐threatening complications such as the hemolytic‐uremic syndrome (HUS). HUS patients frequently have elevated levels of the proinflammatory cytokine tumor necrosis factor α (TNF‐α) detectable in urine. Thus, sequelae may develop following the localized production of proinflammatory cytokines within the kidneys. A possible source of these cytokines are macrophages, which respond to the toxins by producing TNF‐α. We have shown previously that THP‐1 cells produce soluble TNF‐α in response to the toxins, whose production requires host‐cell tyrosine‐kinase activity and toxin‐enzymatic activity. To further examine signaling pathways involved in TNF‐α expression, we determined that JNK1 and ‐2 and p38, but not ERK1 or ‐2, were phosphorylated following toxin exposure. Blockade of p38 activation reduced TNF‐α production following Shiga toxin 1 treatment. Finally, we present a model of the ribotoxic stress response triggered in human macrophages by Shiga toxins.