Huang N, Shaik-Dasthagirisaheb Y B, LaValley M P, Gibson F C
Section of Infectious Diseases, Department of Medicine, Boston University School of Medicine, Boston, MA, USA.
Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
Mol Oral Microbiol. 2015 Dec;30(6):438-50. doi: 10.1111/omi.12103. Epub 2015 Jun 9.
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.
牙周疾病是一类本质上由多种微生物引起的慢性口腔炎症性疾病。龈下菌斑中特定细菌（如牙龈卟啉单胞菌）的存在与微生物群落失调以及宿主免疫反应的调节相关。细菌引发的先天性免疫激活和炎症是导致支持牙齿的软硬组织破坏的关键因素。肝X受体（LXRs）是核激素受体，在脂质稳态、炎症以及宿主对感染的反应中具有重要功能；然而，它们对诸如牙周疾病等慢性炎症性疾病的作用尚不清楚。本研究的目的是确定LXRs在针对牙龈卟啉单胞菌的免疫反应发展中的作用，并评估LXRs在感染引发的口腔骨质流失中所起的作用。利用巨噬细胞，我们观察到与未受挑战的野生型细胞相比，牙龈卟啉单胞菌刺激导致LXRα和LXRβ基因表达降低。髓样分化初级反应基因88（MyD88）非依赖性、含Toll/白细胞介素-1受体结构域的衔接蛋白诱导干扰素-β（TRIF）依赖性信号传导影响牙龈卟啉单胞菌介导的LXRα表达降低，而这两条途径均未影响牙龈卟啉单胞菌对LXRβ表达的作用。利用LXR激动剂和LXR基因缺陷小鼠，我们观察到LXRs在巨噬细胞水平上对牙龈卟啉单胞菌引发的细胞因子反应发展中的功能作用，以及LXRs参与牙龈卟啉单胞菌引发的口腔骨质流失。这些发现确定了LXRs在牙龈卟啉单胞菌感染引发的炎症和口腔骨质流失发病机制中的新重要性。
