Department of Operative Dentistry and Endodontics, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong, 510055, China.
Inflammation. 2015 Apr;38(2):566-75. doi: 10.1007/s10753-014-9963-5.
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.
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。