title: Porphyromonas gingivalis lipopolysaccharide is poorly recognized by molecular components of innate host defense in a mouse model of early inflammation.
abstract: Porphyromonas gingivalis is a gram-negative bacterium that is associated with periodontitis. It has been hypothesized that destruction of bone and periodontal connective tissue is associated with colonization of the subgingival crevicular space by P. gingivalis, although how these bacteria overcome innate host defenses is largely unknown. To examine the early cellular and molecular events of P. gingivalis interaction with host tissues, we compared lipopolysaccharide (LPS) isolated from this bacterium with Escherichia coli LPS, a potent inflammatory mediator, in a mouse model of acute inflammation. In these studies, mice were given intramuscular injections of either P. gingivalis LPS or E. coli LPS and then sacrificed after 4 h. Reverse transcriptase-PCR analysis showed that expression of mRNAs for E- and P-selectins was higher in E. coli LPS-injected muscles than in P. gingivalis LPS-injected or control phosphate-buffered-saline-injected muscles. Similarly, monocyte chemotactic protein 1 and fibroblast-induced cytokine mRNAs were expressed in E. coli LPS-injected muscles whereas their expression was reduced or absent in P. gingivalis LPS-injected samples. These results were confirmed by in situ hybridization whereby stronger hybridization for selectin mRNAs was observed in the endothelium of capillaries from E. coli LPS-injected samples than in that from P. gingivalis LPS-injected muscles. In addition, many monocytes expressing monocyte chemotactic protein 1 mRNA and polymorphonuclear leukocytes expressing fibroblast-induced cytokine mRNA were observed in E. coli LPS-injected muscles whereas only a few cells were identified in P. gingivalis LPS-injected muscles. These results demonstrate that compared with E. coli, P. gingivalis has a low biologically reactive LPS as measured by its weak activation of inflammation. This may allow P. gingivalis to evade innate host defense mechanisms, resulting in colonization and chronic disease.
authors.affiliation: Bristol-Myers Squibb, Pharmaceutical Research Institute, Seattle, Washington 98121, USA.
authors.forename: R A
authors.initials: RA
authors.lastname: Reife
authors.forename: R A
authors.initials: RA
authors.lastname: Shapiro
authors.forename: B A
authors.initials: BA
authors.lastname: Bamber
authors.forename: K K
authors.initials: KK
authors.lastname: Berry
authors.forename: G E
authors.initials: GE
authors.lastname: Mick
authors.forename: R P
authors.initials: RP
authors.lastname: Darveau
mesh_terms: D000818:Animals; D001483:Base Sequence; D018932:Chemokine CCL2 / Q000235:genetics; D016207:Cytokines / Q000235:genetics; D004195:Disease Models, Animal; D019040:E-Selectin / Q000235:genetics; D004926:Escherichia coli / Q000472:pathogenicity; D007249:Inflammation / Q000276:immunology* / Q000382:microbiology; D008070:Lipopolysaccharides / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D019007:P-Selectin / Q000235:genetics; D016133:Polymerase Chain Reaction; D016966:Porphyromonas gingivalis / Q000276:immunology* / Q000472:pathogenicity; D012333:RNA, Messenger / Q000032:analysis
chemical_list: D018932:Chemokine CCL2; D016207:Cytokines; D019040:E-Selectin; D008070:Lipopolysaccharides; D019007:P-Selectin; D012333:RNA, Messenger