Liver X receptors contribute to periodontal pathogen-elicited inflammation and oral bone loss

• Published in: Molecular oral microbiology Vol. 30; no. 6; pp. 438 - 450
• Main Authors: Huang, N., Shaik-Dasthagirisaheb, Y.B., LaValley, M.P., Gibson III, F.C.
• Format: Journal Article
• Language: English
• Published: Denmark Blackwell Publishing Ltd 01.12.2015; Wiley Subscription Services, Inc
• Subjects: Adaptor Proteins, Vesicular Transport - genetics; Alveolar Bone Loss - immunology; Alveolar Bone Loss - microbiology; Alveolar Bone Loss - physiopathology; Animals; Bacteroidaceae Infections - immunology; Bacteroidaceae Infections - metabolism; Bacteroidaceae Infections - microbiology; Cells, Cultured; cytokine; Cytokines - genetics; Dentistry; Immunity, Innate; Inflammation; innate immunity; Interferon Regulatory Factor-3 - genetics; liver X receptor; Liver X Receptors; macrophage; Macrophages - immunology; Macrophages - metabolism; Macrophages - microbiology; Mice; Mice, Inbred C57BL; Mice, Knockout; Myeloid Differentiation Factor 88 - genetics; oral bone loss; Orphan Nuclear Receptors - agonists; Orphan Nuclear Receptors - genetics; Orphan Nuclear Receptors - metabolism; Periodontal Diseases; Porphyromonas gingivalis; Porphyromonas gingivalis - immunology; Signal Transduction - genetics; Toll-Like Receptor 2 - genetics; Tumor Necrosis Factor-alpha - genetics; Porphyromonas gingivalis; cytokine; macrophage; oral bone loss; innate immunity; liver X receptor
• ISSN: 2041-1006; 2041-1014
• DOI: 10.1111/omi.12103

Summary 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.