Role of virulence factors, cell components and adhesion in Helicobacter pylori-mediated iNOS induction in murine macrophages.
To investigate the mechanisms involved in Helicobacter pylori-mediated inducible nitric oxide synthase (iNOS) upregulation in mononuclear cells we cocultivated human THP-1 acute monocytic leukemia cells and murine J774A.1 professional macrophages with different H. pylori wild-type strains and mutants. We have shown that H. pylori-mediated iNOS induction in J774A.1 is independent of established virulence factors but dependent on direct interaction between bacteria and cells. In J774A.1, iNOS was equally upregulated by the wild-type strains J99, 26695, P12, and P1 as well as by mutants lacking the cag pathogenicity island, vacA, katA, alpAB genes and the hp0043 gene taking part in lipopolysaccharide biosynthesis when direct cell contact was allowed but not when bacteria and cells were separated by protein-permeable filter membranes. In contrast, iNOS was not induced in THP-1. This indicates that H. pylori-mediated iNOS induction in J774A.1 is independent of important virulence factors whereas cell contact is crucial which suggests a role of adhesion or phagocytosis.
Department of Surgery, Klinikum Grosshadern, Ludwig-Maximilians-University Munich, Germany.
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Assmann
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Enders
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Püls
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Rieder
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Haas
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Hatz
D000818:Animals; D001422:Bacterial Adhesion / Q000502:physiology; D001426:Bacterial Proteins / Q000494:pharmacology*; D004790:Enzyme Induction; D016480:Helicobacter pylori / Q000472:pathogenicity*; D006801:Humans; D008074:Lipoproteins / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology* / Q000382:microbiology; D051379:Mice; D019001:Nitric Oxide Synthase / Q000096:biosynthesis* / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D012333:RNA, Messenger / Q000096:biosynthesis; D014407:Tumor Cells, Cultured; D037521:Virulence Factors
D001426:Bacterial Proteins; D008074:Lipoproteins; D012333:RNA, Messenger; D037521:Virulence Factors; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse