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大鼠牙髓中的黑色素瘤缺失因子2(AIM2)在牙髓炎期间介导炎症反应。

Absent in melanoma 2 (AIM2) in rat dental pulp mediates the inflammatory response during pulpitis.

作者信息

Wang Yafei, Zhai Shafei, Wang Haijing, Jia Qian, Jiang Wenkai, Zhang Xiao, Zhang Ansheng, Liu Jun, Ni Longxing

机构信息

Department of Operative Dentistry and Endodontics, School of Stomatology, Fourth Military Medical University, Shaanxi, China.

出版信息

J Endod. 2013 Nov;39(11):1390-4. doi: 10.1016/j.joen.2013.07.003. Epub 2013 Sep 4.

Abstract

INTRODUCTION

In recent years, the inflammasome has been determined to play an important role in inflammatory diseases. However, the role of the inflammasome in pulpitis remains unclear. Absent in melanoma 2 (AIM2) is a type of inflammasome that recognizes cytosolic double stranded DNA and forms a caspase-1-activating inflammasome with apoptosis-associated speck-like protein containing a caspase activating recruiting domain. In this study, we determined whether AIM2 was expressed in pulp cells and defined the role of AIM2 in the initiation of inflammation within the dental pulp.

METHODS

In the in vivo study, the right maxillary molars from male adult Sprague-Dawley rats (250-350 g) were exposed to the pulp. In the in vitro study, the pulp cells isolated from the mandibular incisors of the Sprague-Dawley rats (2 weeks) were conventionally cultured. Immunofluorescence staining was used to determine the expression and distribution of AIM2 in the rat dental pulp tissues and cells in the presence or absence of inflammatory stimulation. Western blotting and real-time polymerase chain reaction were performed to determine whether there was a correlation between AIM2 expression levels and inflammation both in vivo and in vitro.

RESULTS

In healthy dental pulp tissues and cells, AIM2 was only detected in the odontoblast layer. Stimulation significantly increased AIM2 expression in both the dental pulp tissues and cultured cells. The mRNA and protein levels of AIM2 were significantly up-regulated in response to inflammatory stimulation in a dose-dependent manner. Moreover, we also found that AIM2 expression correlated with interleukin-1 levels. These results reveal a direct relationship between the AIM2 inflammasome and pulpitis.

CONCLUSIONS

Our study demonstrates that AIM2 is expressed in dental pulp tissues and mediates the inflammatory response during pulpitis. Therapeutic interventions aimed at reducing AIM2 expression may be beneficial in the treatment of pulpitis.

摘要

引言

近年来,已确定炎性小体在炎症性疾病中起重要作用。然而,炎性小体在牙髓炎中的作用仍不清楚。黑色素瘤缺乏因子2(AIM2)是一种炎性小体,可识别胞质双链DNA,并与含有半胱天冬酶激活招募结构域的凋亡相关斑点样蛋白形成激活半胱天冬酶-1的炎性小体。在本研究中,我们确定了AIM2是否在牙髓细胞中表达,并明确了AIM2在牙髓炎症起始中的作用。

方法

在体内研究中,将成年雄性Sprague-Dawley大鼠(250-350 g)的右上颌磨牙暴露牙髓。在体外研究中,常规培养从Sprague-Dawley大鼠(2周龄)下颌切牙分离的牙髓细胞。使用免疫荧光染色确定在有无炎症刺激情况下AIM2在大鼠牙髓组织和细胞中的表达及分布。进行蛋白质免疫印迹和实时聚合酶链反应,以确定体内和体外AIM2表达水平与炎症之间是否存在相关性。

结果

在健康牙髓组织和细胞中,仅在成牙本质细胞层检测到AIM2。刺激显著增加了牙髓组织和培养细胞中AIM2的表达。AIM2的mRNA和蛋白质水平在炎症刺激下呈剂量依赖性显著上调。此外,我们还发现AIM2表达与白细胞介素-1水平相关。这些结果揭示了AIM2炎性小体与牙髓炎之间的直接关系。

结论

我们的研究表明,AIM2在牙髓组织中表达,并在牙髓炎期间介导炎症反应。旨在降低AIM2表达的治疗干预可能对牙髓炎的治疗有益。

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