title: Helicobacter pylori induces interleukin-8 expression in endothelial cells and the signal pathway is protein tyrosine kinase dependent.
abstract: Helicobacter pylori (HP) infection has been shown to increase gastric mucosal interleukin 8 (IL-8) expression, and whether HP or its toxin induces endothelial cell IL-8 expression is unknown. We aimed to compare the IL-8 expression in endothelial cells after stimulation with HP toxin, tumor necrosis factor alpha (TNF-alpha), and lipopolysaccharide (LPS) and to study their signal pathways. HP or its toxin induced significant IL-8 expression in endothelial cells. HP toxin, TNF-alpha, and LPS also showed a time- and dose-dependent increase in IL-8 expression over the control. Both protein kinase C (PKC) and protein kinase A (PKA) inhibitors had no effect on IL-8 response to these stimuli. Protein tyrosine kinase (PTK) inhibitor genistein at concentrations of 150, 300, and 450 microM dose-dependently reduced LPS- and TNF-alpha-induced IL-8 expression by 29.43, 43.8, and 47.3% and 20.5, 49.9, and 61.8% respectively, whereas HP toxin-induced IL-8 secretion could only be reduced at 450 microM by 35.7%. Geldanamycin, a more potent PTK inhibitor, at doses of 0.5, 1, and 2 microM dose-dependently reduced HP toxin induced endothelial cell IL-8 expression by 24.8, 26, and 44.3% respectively. It is concluded that HP and its toxin can increase IL-8 expression in endothelial cells, and the expression of IL-8 elicited by HP toxin, TNF-alpha, and LPS is partially dependent on PTK but not PKA or PKC activation.
authors.affiliation: Department of Medicine, University of Hong Kong, China.
authors.forename: S Z
authors.initials: SZ
authors.lastname: Ding
authors.forename: C H
authors.initials: CH
authors.lastname: Cho
authors.forename: S K
authors.initials: SK
authors.lastname: Lam
mesh_terms: D001426:Bacterial Proteins / Q000494:pharmacology*; D001427:Bacterial Toxins / Q000494:pharmacology*; D016227:Benzoquinones; D002460:Cell Line; D002470:Cell Survival; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D003603:Cytotoxins / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019833:Genistein / Q000494:pharmacology; D016480:Helicobacter pylori / Q000472:pathogenicity*; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis*; D047029:Lactams, Macrocyclic; D008070:Lipopolysaccharides / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011809:Quinones / Q000494:pharmacology; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D001426:Bacterial Proteins; D001427:Bacterial Toxins; D016227:Benzoquinones; D003603:Cytotoxins; D004791:Enzyme Inhibitors; D016209:Interleukin-8; D047029:Lactams, Macrocyclic; D008070:Lipopolysaccharides; D011809:Quinones; D014409:Tumor Necrosis Factor-alpha; C074689:VacA protein, Helicobacter pylori; D019833:Genistein; D011505:Protein-Tyrosine Kinases; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; C001277:geldanamycin