Zeste基因增强子人类同源物2抑制剂GSK343调节巨噬细胞分化的作用

doi:10.7518/hxkq.2017.03.007

华西口腔医学杂志 ›› 2017, Vol. 35 ›› Issue (3): 264-268.doi: 10.7518/hxkq.2017.03.007

Zeste基因增强子人类同源物2抑制剂GSK343调节巨噬细胞分化的作用

王忠朝^1,²(), 范丽苑^1,³, 谭丹^1,², 周骢^1,², 罗世君^1,³

1.西南医科大学口颌面修复重建和再生实验室
2.西南医科大学附属口腔医院口腔内科
3.修复科,泸州 646000

收稿日期:2016-11-05 修回日期:2017-01-02 出版日期:2017-06-05 发布日期:2017-06-01
作者简介:
王忠朝,主治医师,硕士,E-mail：9333829@qq.com
基金资助:
泸州市科技局基金[2016-S-66(1/3)]

Therapeutic effect of enhancer of Zeste homolog 2 inhibitor GSK343 on periodontitis by regulating macrophage diffe-rentiation

Zhongchao Wang^1,²(), Liyuan Fan^1,³, Dan Tan^1,², Cong Zhou^1,², Shijun Luo^1,³

1. Orofacial Reconstruction and Regeneration Laboratory, Southwest Medical University, Luzhou 646000, China
2. Dept. of Oral Medicine, The Affiliated Stomatological Hospital of Southwest Medical University, Luzhou 646000, China
3. Dept. of Prosthodontics, The Affiliated Stomatological Hospital of Southwest Medical University, Luzhou 646000, China

Received:2016-11-05 Revised:2017-01-02 Online:2017-06-05 Published:2017-06-01
Supported by:
Supported by: Fund of Science and Technology Bureau of Luzhou [2016-S-66(1/3)].

摘要/Abstract

摘要：

目的研究Zeste基因增强子人类同源物2（EZH2）抑制剂GSK343调节巨噬细胞亚群的分化,探讨EZH2在牙周炎中潜在的治疗作用。方法将巨噬细胞RAW264.7分为4组：空白组（A组）、对照组（B组）、内毒素（LPS）刺激组（C组）、LPS+GSK343组（D组）。细胞经培养及相应处理后,利用免疫印迹和酶联免疫吸附试验检测其表型生物学标志变化,包括肿瘤坏死因子-α（TNF-α）、诱导型一氧化氮合酶（iNOS）、白细胞介素-10（IL-10）和精氨酸酶-1（Arg-1）。利用大肠杆菌吞噬试验检测巨噬细胞RAW264.7在不同条件下对大肠杆菌的吞噬作用。结果 LPS可以诱导RAW264.7产生M1表型生物标志（TNF-α和iNOS表达增加）,在加入EZH2抑制GSK343后,IL-10和Arg-1表达升高,提示EZH2抑制剂GSK343可以诱导RAW264.7细胞由M1型向M2型转化;RAW264.7细胞具有吞噬大肠杆菌的作用,加入LPS的条件下吞噬大肠杆菌作用加强,而EZH2抑制剂GSK343可以调节RAW264.7细胞对大肠杆菌的吞噬作用。结论 EZH2抑制剂GSK343可以调节巨噬细胞的分化,在牙周炎的治疗中可能具有潜在作用。

关键词: 巨噬细胞, 牙周炎, 表观遗传学, 微环境

Abstract:

Objective To explore the therapeutic effect of enhancer of Zeste homolog 2 (EZH2) inhibitor GSK343 on periodontitis by regulating microphage differentiation. Methods Macrophage RAW264.7 cells were divided into the blank (A group), control (B group), lipopolysaccharide (LPS) stimulation (C group), and LPS+GSK343 (D group) groups. Phenotype transformations was determined through Western blot analysis and enzyme-linked immunosorbent assay by detecting the differentiation of phenotypic biological markers, including tumor necrosis factor-α (TNF-α), inducible nitric oxide synthase (iNOS), interleukin-10 (IL-10), and Arginase-1 (Arg-1). Metergasis was identified by performing a phagocytosis test on Esche-richia coli (E. coli). Results Macrophage RAW264.7 cells produced classical phenotypic biomarkers (M1) TNF-α and iNOS under LPS stimulation. The expression levels of IL-10 and Arg-1 increased after adding GSK343 into the culture medium. GSK343 also induced the conversion of M1 macrophages into M2 macrophages. Macrophage RAW264.7 cells exerted a phagocytic effect on E. coli, and this effect was enhanced after adding LPS into the culture medium. GSK343 regulated the macrophage RAW264.7 phagocytosis of E. coli. Conclusion GSK343 possibly participates in the regulation of macrophage differentiation and, consequently, in the latent treatment of periodontitis.

Key words: macrophage, periodontitis, epigenetic, microenvironment

中图分类号:

R 780.2

王忠朝, 范丽苑, 谭丹, 周骢, 罗世君. Zeste基因增强子人类同源物2抑制剂GSK343调节巨噬细胞分化的作用[J]. 华西口腔医学杂志, 2017, 35(3): 264-268.

Zhongchao Wang, Liyuan Fan, Dan Tan, Cong Zhou, Shijun Luo. Therapeutic effect of enhancer of Zeste homolog 2 inhibitor GSK343 on periodontitis by regulating macrophage diffe-rentiation[J]. West China Journal of Stomatology, 2017, 35(3): 264-268.

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Zeste基因增强子人类同源物2抑制剂GSK343调节巨噬细胞分化的作用

Therapeutic effect of enhancer of Zeste homolog 2 inhibitor GSK343 on periodontitis by regulating macrophage diffe-rentiation

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