Liver X receptors contribute to periodontal pathogen-elicited inflammation and oral bone loss.
Liver X receptors contribute to periodontal pathogen-elicited inflammation and oral bone loss.
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DOI：
10.1111/omi.12103
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发表时间：
2015-12
影响因子：
3.7
通讯作者：
Gibson FC 3rd
中科院分区：
文献类型：
--
作者：
Huang N;Shaik-Dasthagirisaheb YB;LaValley MP;Gibson FC 3rd
牙周病是一种慢性口腔炎症性疾病，本质上是多菌的。牙龈下菌斑中特定细菌的存在与微生物的失调和宿主免疫反应的调节有关。细菌引发的先天免疫激活和炎症是破坏支撑牙齿的软硬组织的关键因素。肝X受体(LXRs)是一种核激素受体，在脂质平衡、炎症和宿主对感染的反应中具有重要作用；然而，它们在牙周病等慢性炎症性疾病中的作用尚不清楚。这项研究的目的是确定LXRs在牙龈假单胞菌免疫反应发展中的作用，并评估LXRs在感染引起的口腔骨丢失中所起的作用。利用巨噬细胞，我们观察到，与未被攻击的野生型细胞相比，牙龈假单胞菌攻击导致LxRα和LxRβ基因表达降低。髓系分化初级反应基因88(MyD88)不依赖于TIR结构域、TIR结构域依赖的适配器诱导干扰素-β(TRIF)依赖的信号转导影响牙龈假单胞菌介导的LXRα表达的降低，而这两条途径都不影响牙龈假单胞菌对LXRβ表达的影响。利用LXR激动剂和LXRs缺陷小鼠，在巨噬细胞水平上观察了LXRs在牙龈假单胞菌诱导的细胞因子反应中的功能作用，以及LXRs参与了Pgg诱导的口腔骨丢失。这些发现确定了LXRs在牙龈假单胞菌感染引起的炎症和口腔骨质丢失的发病机制中的新的重要性。
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 modulation of host immune response. Bacteria-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 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 to that observed with unchallenged wild type cells. Myeloid differentiation primary response gene 88 (MyD88)-independent, TIR-domain-containing adapter-inducing interferon-β (TRIF)-dependent signaling affected P. gingivalis-mediated reduction in LXRα expression, while 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 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.