尼古丁和牙龈卟啉单胞菌脂多糖影响单核细胞黏附血管内皮细胞的分子机制

doi:10.3969/j.issn.1671-167X.2015.05.015

北京大学学报(医学版) ›› 2015, Vol. 47 ›› Issue (5): 809-813. doi: 10.3969/j.issn.1671-167X.2015.05.015

尼古丁和牙龈卟啉单胞菌脂多糖影响单核细胞黏附血管内皮细胞的分子机制

王衣祥1，安娜2△，欧阳翔英3

（北京大学口腔医学院·口腔医院1. 中心实验室，2.综合二科，3.牙周科，北京100081）

出版日期:2015-10-18 发布日期:2015-10-18
通讯作者: 安娜 E-mail:anna@pkuss.bjmu.edu.cn
基金资助:
科技部国际合作计划基金（1019）资助

Molecular mechanism involved in adhesion of monocytes to endothelial cells induced by nicotine and Porphyromonas gingivalis-LPS

WANG Yi-xiang1, AN Na2△, OUYANG Xiang-ying3

(1.Central Laboratory, 2. Department of General Dentistry Ⅱ, 3. Department of Periodontology, Peking University School and Hospital of Stomatology, Beijing 100081, China)

Online:2015-10-18 Published:2015-10-18
Contact: AN Na E-mail:anna@pkuss.bjmu.edu.cn
Supported by:
Supported by International Science & Technology Cooperation Program Foundation in Ministry of Science & Technology of China (1019)

摘要/Abstract

摘要：

目的：研究牙龈卟啉单胞菌和尼古丁影响动脉粥样硬化的初步分子机制。方法：在单核细胞U937细胞中，用CCK-8法检测尼古丁、牙龈卟啉单胞菌脂多糖（Porphyromonas gingivalis lipopolysaccharide，P.g-LPS）及二者联合对U937细胞增殖能力的影响；实时定量荧光聚合酶链反应（Real-time PCR）检测尼古丁对P.g-LPS诱导炎症因子白细胞介素（interleukin, IL）-6能力的影响。在血管内皮细胞中，用Real-time PCR和蛋白印记杂交实验检测尼古丁、P.g-LPS及二者联合应用对单核细胞趋化因子（C-C模体）配体8 ［chemokine (C-C motif) ligand 8, CCL-8］和血管细胞黏附因子1（vascular cell adhesion molecule 1，Vcam-1）、非常晚期抗原4α（very late antigen 4 alpha，VLA4α）、肿瘤坏死因子受体超家族成员4（tumor necrosis factor receptor superfamily member 4，OX40）和其配体（OX40 ligand，OX40L）的表达的影响。同时，在尼古丁和P.g-LPS共同作用下，用黏附实验检测单核细胞与血管内皮细胞的黏附能力。结果：P.g-LPS并不影响尼古丁促进单核细胞系U937增殖的作用，100 μmol/L尼古丁能抑制P.g-LPS诱导U937细胞产生IL-6的能力。在血管内皮细胞中，与对照和单一药物处理相比，尼古丁和P.g-LPS共同作用可以促进其表达CCL-8及Vcam-1、VLA4α、OX40和OX40L。黏附实验结果显示，尼古丁和P.g-LPS共同刺激可以明显提高单核细胞黏附血管内皮细胞的能力。结论：牙龈卟啉单胞菌和尼古丁可能通过上调CCL-8表达募集单核细胞到血管内皮损伤处，并通过增强黏附分子Vcam1/VLA4α及OX40L/OX40的相互作用，促进单核细胞与血管内皮细胞黏附，参与动脉粥样硬化病损的启动和形成。

关键词: 尼古丁, 牙龈卟啉单胞菌, 动脉粥样硬化, 细胞黏附分子

Abstract:

Objective： To investigate molecular mechanism involved in nicotine in combination with Porphyromonas gingivalis (P.g) caused monocyte-endothelial cell adhesion. Methods: The effect of nicotine, P.g-lipopolysaccharide (P.g-LPS) and their combination on the proliferation of U937 cells was determined by CCK-8 method. Interleukin-6 (IL-6) expression was investigated by Real-time PCR after U937 cells were treated with nicotine, P.g-LPS and their combination. In human umbilical vein endothelial cells (HUVECs), the expressions of monocyte chemoattractant protein CCL-8 and adhesion molecules including vascular cell adhesion molecule 1 (Vcam-1), very late antigen 4 alpha (VLA4α), tumor necrosis factor receptor superfamily member 4 (OX40) and OX40 ligand (OX40L) were detected by Real-time PCR or Western blotting assays after HUVEC cells were treated with nicotine, P.g-LPS and their combination. Adhesion of monocytes to endothelial cells was detected after the HUVECs and U937 cells were stimulated with nicotine, P.g-LPS and their combination, respectively. Results: P.g-LPS did not affect the proliferative ability of nicotine in U937 cells. However, the ability of P.g-LPS induced IL-6 expression was inhibited by 100 μmol/L nicotine in U937 cells. In HUVECs, the expressions of CCL-8, Vcam-1, VLA4α, OX40 and OX40L were significantly up-regulated by nicotine and P.gLPS combination compared with nicotine alone, P.g-LPS alone and the untreated control. Adhesion of monocytes to HUVECs results showed that the two types of cells treated with nicotine in combination with P.g-LPS could markedly increase the adhesion ability of monocytes to HUVECs. Conclusion: P.g-LPS in combination with nicotine could recruit monocytes to endothelial lesion through up-regulation of CCL-8, and promote adhesion of monocytes to endothelial cells through enhancement of Vcam-1/VLA4α and OX40/OX40L interactions, which could be involved in the initiation and development of atherosclerosis.

Key words: Nicotine, Porphyromonas gingivalis, Atherosclerosis, Cell adhesion molecules

中图分类号:

R781.42

王衣祥，安娜，欧阳翔英. 尼古丁和牙龈卟啉单胞菌脂多糖影响单核细胞黏附血管内皮细胞的分子机制[J]. 北京大学学报(医学版), 2015, 47(5): 809-813.

WANG Yi-xiang, AN Na, OUYANG Xiang-ying. Molecular mechanism involved in adhesion of monocytes to endothelial cells induced by nicotine and Porphyromonas gingivalis-LPS[J]. Journal of Peking University(Health Sciences), 2015, 47(5): 809-813.

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尼古丁和牙龈卟啉单胞菌脂多糖影响单核细胞黏附血管内皮细胞的分子机制

Molecular mechanism involved in adhesion of monocytes to endothelial cells induced by nicotine and Porphyromonas gingivalis-LPS

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