title: Response of human macrophage-like cells to stimulation by Fusobacterium nucleatum ssp. nucleatum lipopolysaccharide.
abstract: Monocytes/macrophages are key members of the innate immune system and are present in higher numbers in active periodontal lesions than in inactive sites. The aim of this study was to characterize the response of human monocyte U937 cells, differentiated into adherent macrophages by treatment with phorbol-12-myristate 13-acetate, to stimulation by Fusobacterium nucleatum ssp. nucleatum lipopolysaccharide. Attachment of (3)H-lipopolysaccharide to macrophage-like cells was partially inhibited by anti-CD14 and anti-TLR4 polyclonal antibodies. Fusobacterial lipopolysaccharide did not cause cell apoptosis or block apoptosis induced by camptothecin. Lipopolysaccharide up-regulated the secretion of the pro-inflammatory cytokines interleukin-1beta, interleukin-6, and tumor necrosis factor-alpha as well as the chemokine interleukin-8 by macrophage-like cells. In addition, it increased phospholipase C and D activities, which likely contributed to the high levels of prostaglandin E(2) detected in the cell culture supernatant. Lastly, the amount of matrix metalloproteinase-9 produced by macrophage-like cells was significantly increased by the lipopolysaccharide treatment. Interestingly, fusobacterial cells acquired matrix metalloproteinase-9 activity following incubation in the presence of the culture supernatant of lipopolysaccharide-stimulated macrophage-like cells. In summary, the lipopolysaccharide of F. nucleatum ssp. nucleatum has a large array of biological effects on macrophage-like cells. This monocytic responsiveness to lipopolysaccharide may be a key regulator of periodontitis.
authors.affiliation: Groupe de Recherche en Ecologie Buccale, Faculté de Médecine Dentaire, Université Laval, Quebec City, Quebec, Canada. daniel.grenier@greb.ulaval.ca
authors.forename: D
authors.initials: D
authors.lastname: Grenier
authors.forename: L
authors.initials: L
authors.lastname: Grignon
mesh_terms: D017209:Apoptosis; D016207:Cytokines / Q000096:biosynthesis; D015232:Dinoprostone / Q000096:biosynthesis; D016967:Fusobacterium nucleatum / Q000276:immunology*; D006801:Humans; D008070:Lipopolysaccharides / Q000276:immunology; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D009000:Monocytes / Q000187:drug effects; D009569:Nitric Oxide / Q000096:biosynthesis; D010518:Periodontitis / Q000276:immunology; D010740:Phospholipases / Q000096:biosynthesis; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D020298:U937 Cells; D015854:Up-Regulation
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides; D009569:Nitric Oxide; D010740:Phospholipases; D020780:Matrix Metalloproteinase 9; D015232:Dinoprostone; D013755:Tetradecanoylphorbol Acetate