Extracellular vesicles of P. gingivalis-infected macrophages induce lung injury.
Extracellular vesicles of P. gingivalis-infected macrophages induce lung injury.
复制标题
牙龈卟啉单胞菌感染的巨噬细胞的细胞外囊泡诱导肺损伤。
DOI：
10.1016/j.bbadis.2021.166236
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发表时间：
2021
期刊：
影响因子：
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通讯作者：
Kazumi Ozaki
中科院分区：
文献类型：
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作者：
Kayo Yoshida;Kaya Yoshida;Natsumi Fujiwara;Mariko Seyama;Kisho Ono;Hotaka Kawai;Jiajie Guo;Ziyi Wang;Yao Weng;Yaqiong Yu;Yoko Uchida-Fukuhara;Mika Ikegame;Akira Sasaki;Hitoshi Nagatsuka;Hiroshi Kamioka;Hirohiko Okamura;Kazumi Ozaki
牙周病是由牙龈卟啉单胞菌（Porphyromonas gingivalis，Pg）等牙周细菌感染引起的常见炎症性疾病。牙周病和许多类型的全身性疾病之间的关联已经被证明;术语“牙周医学”用于描述牙周感染/炎症如何影响口腔外健康。然而，口腔中产生的因子到达多个远端器官并影响总体健康的分子机制尚未阐明。细胞外囊泡（extracellular vesicles，EV）是由各种类型的细胞分泌到组织微环境中的纳米尺寸的球形结构，并且通过递送它们的货物来影响病理生理条件。然而，对电动汽车对牙周医学的影响缺乏详细的了解。在这项研究中，我们研究了是否来自Pg感染的巨噬细胞的EV到达小鼠的远端器官并影响病理生理状态。从感染Pg的人巨噬细胞THP-1细胞中分离到EV，发现感染Pg的THP-1细胞中的EV（Pg-inf EV）含有丰富的核心组蛋白，如组蛋白H3，并可转位到小鼠的肺、肝和肾中，Pg-inf EV还可引起肺损伤，包括水肿、血管充血、炎症和胶原沉积，导致肺泡破坏。Pg-inf EV或重组组蛋白H3激活NF-κB通路，导致人肺上皮A549细胞中促炎细胞因子水平增加。我们的研究结果表明，牙周病中产生的EV有助于牙周医学的进展的可能机制。
Periodontal diseases are common inflammatory diseases that are induced by infection with periodontal bacteria such asPorphyromonas gingivalis(Pg). The association between periodontal diseases and many types of systemic diseases has been demonstrated; the term “periodontal medicine”is used to describe how periodontal infection/inflammation may impact extraoral health. However, the molecular mechanisms by which the factors produced in the oral cavity reach multiple distant organs and impact general health have not been elucidated. Extracellular vesicles (EVs) are nano-sized spherical structures secreted by various types of cells into the tissue microenvironment, and influence pathophysiological conditions by delivering their cargo. However, a detailed understanding of the effect of EVs on periodontal medicine is lacking. In this study, we investigated whether EVs derived fromPg-infected macrophages reach distant organs in mice and influence the pathophysiological status. EVs were isolated from human macrophages, THP-1 cells, infected withPg.We observed that EVs fromPg-infected THP-1 cells (Pg-inf EVs) contained abundant core histone proteins such as histone H3 and translocated to the lungs, liver, and kidneys of mice.Pg-inf EVs also induced pulmonary injury, including edema, vascular congestion, inflammation, and collagen deposition causing alveoli destruction. ThePg-inf EVs or the recombinant histone H3 activated the NF-κB pathway, leading to increase in the levels of pro-inflammatory cytokines in human lung epithelial A549 cells. Our results suggest a possible mechanism by which EVs produced in periodontal diseases contribute to the progression of periodontal medicine.