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人牙髓中缺失的黑色素瘤 2(AIM2)表达,可介导细胞质 DNA 反应性的 IL-1β 分泌。

Absent in melanoma 2 (AIM2) expressed in human dental pulp mediates IL-1β secretion in response to cytoplasmic DNA.

机构信息

Department of Operative Dentistry and Endodontics, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong, 510055, China.

出版信息

Inflammation. 2015 Apr;38(2):566-75. doi: 10.1007/s10753-014-9963-5.

DOI:10.1007/s10753-014-9963-5
PMID:24986444
Abstract

The inflammasome has been determined to play an important role in inflammatory diseases in recent years. Absent in melanoma 2 (AIM2), an inflammasome that recognizes cytoplasmic DNA, has recently been identified as a critical regulator of immune responses. In this study, we explored whether AIM2 was expressed in human dental pulp and defined the role of AIM2 in regulating interleukin (IL)-1β secretion. We demonstrated that AIM2 was only detected in the odontoblast layer of healthy dental pulp, whereas strong expression was observed in inflamed dental pulp. Stimulation with interferon gamma (IFN-γ) and cytoplasmic DNA significantly activated the AIM2 inflammasome and increased IL-1β secretion in human dental pulp cells (HDPCs) in a time- and dose-dependent manner. Moreover, the knockdown of AIM2 downregulated both cleaved-caspase-1 expression and IL-1β release in HDPCs. These results suggest that AIM2 expressed in human dental pulp plays an important role in the immune defense by activating the inflammasome signaling pathway.

摘要

近年来,炎症小体被确定在炎症性疾病中发挥重要作用。缺失在黑色素瘤 2(AIM2)中,一种识别细胞质 DNA 的炎症小体,最近被确定为免疫反应的关键调节因子。在这项研究中,我们探讨了 AIM2 是否在人牙髓中表达,并确定了 AIM2 在调节白细胞介素(IL)-1β分泌中的作用。我们证明,AIM2 仅在健康牙髓的成牙本质细胞层中检测到,而在发炎的牙髓中观察到强烈的表达。干扰素γ(IFN-γ)和细胞质 DNA 的刺激以时间和剂量依赖的方式显著激活 AIM2 炎症小体,并增加人牙髓细胞(HDPCs)中 IL-1β 的分泌。此外,AIM2 的敲低下调了 HDPCs 中裂解半胱天冬酶-1 的表达和 IL-1β 的释放。这些结果表明,人牙髓中表达的 AIM2 通过激活炎症小体信号通路在免疫防御中发挥重要作用。

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本文引用的文献

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Absent in melanoma 2 (AIM2) in rat dental pulp mediates the inflammatory response during pulpitis.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。
J Endod. 2013 Nov;39(11):1390-4. doi: 10.1016/j.joen.2013.07.003. Epub 2013 Sep 4.
2
TLR3 mediates release of IL-1β and cell death in keratinocytes in a caspase-4 dependent manner.TLR3 通过半胱天冬酶-4 依赖性方式介导角质形成细胞中白细胞介素-1β的释放和细胞死亡。
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The Cag pathogenicity island and interaction between TLR2/NOD2 and NLRP3 regulate IL-1β production in Helicobacter pylori infected dendritic cells.
Regen Ther. 2024 Mar 7;27:12-20. doi: 10.1016/j.reth.2024.02.010. eCollection 2024 Dec.
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Cytokine secretion and pyroptosis of cholesteatoma keratinocytes mediated by AIM2 inflammasomes in response to cytoplasmic DNA.AIM2 炎性体介导的细胞质 DNA 引发胆脂瘤角质形成细胞细胞因子分泌和细胞焦亡。
Mol Med Rep. 2021 May;23(5). doi: 10.3892/mmr.2021.11983. Epub 2021 Mar 24.
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Expression of AIM2 in Rheumatoid Arthritis and Its Role on Fibroblast-Like Synoviocytes.AIM2 在类风湿关节炎中的表达及其对成纤维样滑膜细胞的作用。
Mediators Inflamm. 2020 Oct 26;2020:1693730. doi: 10.1155/2020/1693730. eCollection 2020.
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AIM2 Inflammasome's First Decade of Discovery: Focus on Oral Diseases.AIM2 炎性小体的发现十周年:聚焦口腔疾病。
Front Immunol. 2020 Aug 13;11:1487. doi: 10.3389/fimmu.2020.01487. eCollection 2020.
7
NLRP1 and NLRC4 inflammasomes are not responsible for the induction of inflammation in pulp tissues from carious teeth.NLRP1和NLRC4炎性小体并非导致龋牙髓组织炎症的原因。
J Conserv Dent. 2019 Jan-Feb;22(1):12-16. doi: 10.4103/JCD.JCD_195_18.
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