School of Pharmaceutical Sciences, Jilin University, Changchun 130021, China.
Hospital of Stomatology, Jilin University & Jilin Provincial Key Laboratory of Oral Biomedical Engineering, Changchun 130021, China.
Dis Markers. 2022 Mar 16;2022:8583674. doi: 10.1155/2022/8583674. eCollection 2022.
Clinically, the failure of periodontal therapy stems largely from an inability to control the inflammatory response. Resolution of inflammation is an active, energy-requiring repair process, not merely a passive termination of inflammation. AMP-activated protein kinase (AMPK), a key energy sensor, has been shown to negatively regulate inflammatory signaling pathways. Thus, there is a crucial need for new therapeutic strategies to modulate AMPK and to promote enhanced resolution of inflammation. This study is aimed at investigating the anti-inflammatory effects of ETC-1002 through modulating AMPK in periodontitis.
RAW264.7 cells were infected with -LPS in the presence or absence of ETC-1002, following which the expression levels of proinflammatory cytokines and inflammation signaling-related proteins were evaluated by real-time reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting. ETC-1002 was applied in a murine model of periodontitis to determine its anti-inflammatory effect . Histological changes were investigated by hematoxylin and eosin (H&E) staining, the levels of proinflammatory cytokines were detected using immunohistochemistry, and alveolar bone height was measured using micro-CT imaging.
ETC-1002 inhibited the production of proinflammatory cytokines, promoted AMPK phosphorylation, and decreased IB and NF-B p65 phosphorylation levels in -LPS-treated RAW264.7 macrophages. The inhibitory effects of ETC-1002 on the production of proinflammatory mediators were significantly abrogated by siRNA-mediated silencing of AMPK in RAW264.7 cells. , ETC-1002 inhibited inflammatory cell infiltration, the expression of proinflammatory cytokines, and the inflammation-mediated destruction of alveolar bone in mice with experimental periodontitis. The anti-inflammatory effect of ETC-1002 in the periodontium could be reversed by the administration of Compound C, an AMPK inhibitor.
ETC-1002 exerts anti-inflammatory effects in -LPS-treated RAW264.7 cells the AMPK/NF-B pathway and inhibits the progress of experimental periodontitis in mice in an AMPK signaling-dependent manner . These results provide evidence for the beneficial effects of ETC-1002 in the treatment of periodontitis.
临床上，牙周病治疗的失败在很大程度上是由于无法控制炎症反应。炎症的消退是一个积极的、需要能量的修复过程，而不仅仅是炎症的被动终止。AMP 激活的蛋白激酶（AMPK），一种关键的能量传感器，已被证明可负向调节炎症信号通路。因此，迫切需要新的治疗策略来调节 AMPK，促进炎症的消退。本研究旨在通过调节牙周炎中的 AMPK 来研究 ETC-1002 的抗炎作用。
RAW264.7 细胞在 LPS 的存在或不存在下被感染，然后通过实时逆转录定量聚合酶链反应（RT-qPCR）和蛋白质印迹法评估促炎细胞因子和炎症信号相关蛋白的表达水平。ETC-1002 应用于牙周炎的小鼠模型中，以确定其抗炎作用。通过苏木精和伊红（H&E）染色观察组织学变化，通过免疫组织化学检测促炎细胞因子的水平，通过微 CT 成像测量牙槽骨高度。
ETC-1002 抑制了 LPS 处理的 RAW264.7 巨噬细胞中促炎细胞因子的产生，促进了 AMPK 的磷酸化，并降低了 IB 和 NF-B p65 的磷酸化水平。在 RAW264.7 细胞中，通过 AMPK 的 siRNA 沉默显著削弱了 ETC-1002 对促炎介质产生的抑制作用。ETC-1002 抑制了实验性牙周炎小鼠的炎症细胞浸润、促炎细胞因子的表达和炎症介导的牙槽骨破坏。在牙周组织中，ETC-1002 的抗炎作用可被 AMPK 抑制剂 Compound C 逆转。
ETC-1002 通过 AMPK/NF-B 通路在 LPS 处理的 RAW264.7 细胞中发挥抗炎作用，并以 AMPK 信号依赖性方式抑制实验性牙周炎小鼠的进展。这些结果为 ETC-1002 在牙周炎治疗中的有益作用提供了证据。
