P38 mitogen-activated protein kinase mediates lipopolysaccharide and tumor necrosis factor alpha induction of shiga toxin 2 sensitivity in human umbilical vein endothelial cells.

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-alpha). The goal of the present study was to identify the intracellular signaling pathway(s) by which LPS and TNF-alpha 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-alpha showed that a relatively short exposure to either agonist was sufficient to se

SUBMITTER: Stone MK 

PROVIDER: S-EPMC2258847 | biostudies-literature | 2008 Mar

REPOSITORIES: biostudies-literature