title: Molecular and functional analysis of Shiga toxin-induced response patterns in human vascular endothelial cells.
abstract: Enterohemorrhagic Escherichia coli (EHEC) is the major cause of hemolyticuremic syndrome (HUS) characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure. EHEC produces one or more Shiga toxins (Stx1 and Stx2), and it was assumed that Stx's only relevant biologic activity was cell destruction through inhibition of protein synthesis. However, recent data indicate that in vivo the cytokine milieu may determine whether endothelial cells survive or undergo apoptosis/necrosis when exposed to Stxs. In this study, we analyzed the genome-wide expression patterns of human endothelial cells stimulated with subinhibitory concentrations of Stxs in order to characterize the genomic expression program involved in the vascular pathology of HUS. We found that Stxs elicited few, but reproducible, changes in gene expression. The majority of genes reported in this study encodes for chemokines and cytokines, which might contribute to the multifaceted inflammatory response of host endothelial cells observed in patients suffering from EHEC disease. In addition, our data provide for the first time molecular insights into the epidemiologically well-established higher pathogenicity of Stx2 over Stx1.
authors.affiliation: Department of Microbiology, German Research Centre for Biotechnology, Braunschweig, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Matussek
authors.forename: Joerg
authors.initials: J
authors.lastname: Lauber
authors.forename: Anna
authors.initials: A
authors.lastname: Bergau
authors.forename: Wiebke
authors.initials: W
authors.lastname: Hansen
authors.forename: Manfred
authors.initials: M
authors.lastname: Rohde
authors.forename: Kurt E J
authors.initials: KE
authors.lastname: Dittmar
authors.forename: Matthias
authors.initials: M
authors.lastname: Gunzer
authors.forename: Michael
authors.initials: M
authors.lastname: Mengel
authors.forename: Patricia
authors.initials: P
authors.lastname: Gatzlaff
authors.forename: Maike
authors.initials: M
authors.lastname: Hartmann
authors.forename: Jan
authors.initials: J
authors.lastname: Buer
authors.forename: Florian
authors.initials: F
authors.lastname: Gunzer
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D018925:Chemokines / Q000096:biosynthesis; D016207:Cytokines / Q000096:biosynthesis / Q000187:drug effects; D017931:DNA Primers / Q000235:genetics; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D004926:Escherichia coli / Q000737:chemistry / Q000472:pathogenicity; D004927:Escherichia coli Infections / Q000503:physiopathology; D005434:Flow Cytometry / Q000379:methods; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D006463:Hemolytic-Uremic Syndrome / Q000503:physiopathology; D006801:Humans; D007150:Immunohistochemistry; D011956:Receptors, Cell Surface / Q000378:metabolism; D022603:Shiga Toxins / Q000494:pharmacology* / Q000633:toxicity; D014281:Trihexosylceramides / Q000378:metabolism; D014471:Umbilical Veins / Q000166:cytology
chemical_list: D018925:Chemokines; D016207:Cytokines; D017931:DNA Primers; D011956:Receptors, Cell Surface; D022603:Shiga Toxins; D014281:Trihexosylceramides; C018549:globotriaosylceramide