title: Porphyromonas gingivalis lipopolysaccharide: an unusual pattern recognition receptor ligand for the innate host defense system.
abstract: Lipopolysaccharide (LPS) is a key inflammatory mediator. Due to its ability to potently activate host inflammatory and innate defense responses, it has been proposed to function as an important molecule that alerts the host of potential bacterial infection. However, although highly conserved, LPS contains important structural differences among different bacterial species that can significantly alter host responses. For example, LPS obtained from Porphyromonas gingivalis, an etiologic agent for periodontitis, causes a highly unusual host innate host response. It is an agonist for human monocytes and an antagonist for human endothelial cells. Correspondingly, although it activates p38 MAP kinase in human monocytes, P. gingivalis LPS does not activate p38 nor ERK MAP kinase in endothelial cells. In fact, P. gingivalis LPS is an effective inhibitor of Escherichia coli LPS induced p38 phosphorylation. These data show that P. gingivalis LPS modulates host defenses in endothelial cells by interfering with MAP kinase activation. In addition, P. gingivalis LPS is unusual in that it engages TLR-2 but not TLR-4 when examined in stably transfected CHO cell lines. We propose that, since LPS is a key ligand for the human innate host defense system, these unusual properties of P. gingivalis LPS are associated with the bacterium's role in the pathogenesis of periodontitis.
authors.affiliation: Department of Periodontics, School of Dentistry, University of Washington, Seattle 98195, USA.
authors.forename: B W
authors.initials: BW
authors.lastname: Bainbridge
authors.forename: R P
authors.initials: RP
authors.lastname: Darveau
mesh_terms: D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D029721:Drosophila Proteins; D004730:Endothelium, Vascular / Q000201:enzymology / Q000276:immunology; D004789:Enzyme Activation / Q000276:immunology; D004926:Escherichia coli / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D018836:Inflammation Mediators / Q000276:immunology; D008024:Ligands; D008070:Lipopolysaccharides / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000276:immunology; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000276:immunology; D009000:Monocytes / Q000201:enzymology / Q000276:immunology; D010518:Periodontitis / Q000276:immunology / Q000382:microbiology; D010766:Phosphorylation; D016966:Porphyromonas gingivalis / Q000276:immunology*; D011956:Receptors, Cell Surface / Q000276:immunology; D011971:Receptors, Immunologic / Q000276:immunology*; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D014162:Transfection; D048051:p38 Mitogen-Activated Protein Kinases
chemical_list: D029721:Drosophila Proteins; D018836:Inflammation Mediators; D008024:Ligands; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases