title: Liver X receptors contribute to periodontal pathogen-elicited inflammation and oral bone loss.
abstract: Periodontal diseases are chronic oral inflammatory diseases that are polymicrobial in nature. The presence of specific bacteria in subgingival plaque such as Porphyromonas gingivalis is associated with microbial dysbiosis and the modulation of host immune response. Bacterially elicited innate immune activation and inflammation are key elements implicated in the destruction of soft and hard tissues supporting the teeth. Liver X receptors (LXRs) are nuclear hormone receptors with important function in lipid homeostasis, inflammation, and host response to infection; however, their contribution to chronic inflammatory diseases such as periodontal disease is not understood. The aim of this study was to define the contribution of LXRs in the development of immune response to P. gingivalis and to assess the roles that LXRs play in infection-elicited oral bone loss. Employing macrophages, we observed that P. gingivalis challenge led to reduced LXRα and LXRβ gene expression compared with that observed with unchallenged wild-type cells. Myeloid differentiation primary response gene 88 (MyD88)-independent, Toll/interleukin-1 receptor-domain-containing adapter-inducing interferon-β (TRIF)-dependent signaling affected P. gingivalis-mediated reduction in LXRα expression, whereas neither pathway influenced the P. gingivalis effect on LXRβ expression. Employing LXR agonist and mice deficient in LXRs, we observed functional effects of LXRs in the development of a P. gingivalis-elicited cytokine response at the level of the macrophage, and participation of LXRs in P. gingivalis-elicited oral bone loss. These findings identify novel importance for LXRs in the pathogenesis of P. gingivalis infection-elicited inflammation and oral bone loss.
authors.affiliation: Section of Infectious Diseases, Department of Medicine, Boston University School of Medicine, Boston, MA, USA.
authors.forename: N
authors.initials: N
authors.lastname: Huang
authors.affiliation: Section of Infectious Diseases, Department of Medicine, Boston University School of Medicine, Boston, MA, USA.
authors.forename: Y B
authors.initials: YB
authors.lastname: Shaik-Dasthagirisaheb
authors.affiliation: Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
authors.forename: M P
authors.initials: MP
authors.lastname: LaValley
authors.affiliation: Section of Infectious Diseases, Department of Medicine, Boston University School of Medicine, Boston, MA, USA.
authors.forename: F C
authors.initials: FC
authors.lastname: Gibson
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics; D016301:Alveolar Bone Loss / Q000276:immunology* / Q000382:microbiology* / Q000503:physiopathology; D000818:Animals; D016866:Bacteroidaceae Infections / Q000276:immunology* / Q000378:metabolism* / Q000382:microbiology; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics; D007113:Immunity, Innate; D007249:Inflammation; D050838:Interferon Regulatory Factor-3 / Q000235:genetics; D000071518:Liver X Receptors; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics; D057093:Orphan Nuclear Receptors / Q000819:agonists / Q000235:genetics* / Q000378:metabolism; D010510:Periodontal Diseases; D016966:Porphyromonas gingivalis / Q000276:immunology*; D015398:Signal Transduction / Q000235:genetics; D051195:Toll-Like Receptor 2 / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D016207:Cytokines; D050838:Interferon Regulatory Factor-3; D000071518:Liver X Receptors; D053594:Myeloid Differentiation Factor 88; D057093:Orphan Nuclear Receptors; D051195:Toll-Like Receptor 2; D014409:Tumor Necrosis Factor-alpha; C494233:Irf3 protein, mouse; C507780:Myd88 protein, mouse; C476286:Ticam1 protein, mouse
keywords: Porphyromonas gingivalis; cytokine; innate immunity; liver X receptor; macrophage; oral bone loss