title: Comparison of the effects of Shiga-like toxin 1 on cytokine- and butyrate-treated human umbilical and saphenous vein endothelial cells.
abstract: To examine the reported heterogeneity of endothelial cells to Shiga-like toxin 1 (Stx1), the responses of human umbilical (HUVEC) and saphenous (HSVEC) vein endothelial cells to cytokines, butyrate, and toxin were compared. Untreated HSVEC were generally more susceptible than were HUVEC to Stx1; pretreatment of either cell with lipopolysaccharide, interleukin-1 beta, or tumor necrosis factor-alpha enhanced Stx1 toxicity. Dexamethasone alone increased total globotriaosylceramide (Gb3) content and toxin binding but inhibited cytokine-enhanced cytotoxicity, whereas the differentiation agent, sodium butyrate, increased both Gb3 content and cytotoxicity responses to Stx1, most prominently in HSVEC. Stx1 toxicity directly correlated with the release of von Willebrand factor from HSVEC but not from HUVEC. Thus, HUVEC and HSVEC exhibit distinctive responses to Stx1, cytokines, and butyrate. This suggests the need for caution in extrapolating from in vitro studies utilizing one endothelial cell type to in vivo events during pathogenesis of Stx-mediated thrombotic microangiopathies.
authors.affiliation: Tupper Research Institute, Division of Geographic Medicine and Infectious Diseases, New England Medical Center, Boston, Massachusetts 02111, USA.
authors.forename: G T
authors.initials: GT
authors.lastname: Keusch
authors.forename: D W
authors.initials: DW
authors.lastname: Acheson
authors.forename: L
authors.initials: L
authors.lastname: Aaldering
authors.forename: J
authors.initials: J
authors.lastname: Erban
authors.forename: M S
authors.initials: MS
authors.lastname: Jacewicz
mesh_terms: D001427:Bacterial Toxins / Q000378:metabolism / Q000633:toxicity*; D002087:Butyrates / Q000494:pharmacology*; D020148:Butyric Acid; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology*; D003603:Cytotoxins / Q000378:metabolism / Q000633:toxicity*; D003907:Dexamethasone / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000737:chemistry / Q000166:cytology* / Q000187:drug effects; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000032:analysis; D012501:Saphenous Vein; D022622:Shiga Toxin 1; D012795:Sialoglycoproteins / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014281:Trihexosylceramides / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014471:Umbilical Veins; D014841:von Willebrand Factor / Q000032:analysis
chemical_list: D001427:Bacterial Toxins; D002087:Butyrates; D016207:Cytokines; D003603:Cytotoxins; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D008070:Lipopolysaccharides; D011956:Receptors, Cell Surface; D022622:Shiga Toxin 1; D012795:Sialoglycoproteins; D014281:Trihexosylceramides; D014409:Tumor Necrosis Factor-alpha; D014841:von Willebrand Factor; D020148:Butyric Acid; C018549:globotriaosylceramide; D003907:Dexamethasone; D013755:Tetradecanoylphorbol Acetate