Molecular and functional analysis of Shiga toxin-induced response patterns in human vascular endothelial cells.
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.
Matussek
Andreas
A
Department of Microbiology, German Research Centre for Biotechnology, Braunschweig, Germany.
Lauber
Joerg
J
Bergau
Anna
A
Hansen
Wiebke
W
Rohde
Manfred
M
Dittmar
Kurt E J
KE
Gunzer
Matthias
M
Mengel
Michael
M
Gatzlaff
Patricia
P
Hartmann
Maike
M
Buer
Jan
J
Gunzer
Florian
F
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
D018925:Chemokines; D016207:Cytokines; D017931:DNA Primers; D011956:Receptors, Cell Surface; D022603:Shiga Toxins; D014281:Trihexosylceramides; C018549:globotriaosylceramide