Zhou Hancheng, Huang Jiaxin, Fan Zixin, Sun Wen, Xu Yan, Li Lu
Department of Periodontics, Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing, 210029, China.
State Key Laboratory Cultivation Base of Research, Prevention and Treatment for Oral Diseases (Nanjing Medical University), Nanjing, 210029, China.
Inflammation. 2024 Oct 22. doi: 10.1007/s10753-024-02168-2.
The role of quorum sensing signaling in the immunoinflammatory response during the development of periodontitis is not yet known. This study aimed to explore the effect of Autoinducer-2, a quorum sensing signaling molecule, on macrophage phenotypic remodeling in the immune microenvironment of periodontitis, to further elucidate its mechanism and to discover inhibitors against periodontitis.
Bioluminescence experiments and periodontitis model were used to demonstrate the association between periodontitis progression with AI-2. Next, AI-2 challenged macrophage was introduced to transcriptomic sequence and the immune profile was characterized in combination with flow cytometry, qPCR, and immunofluorescence. Activation of NF-κB signalling by AI-2 was confirmed by fluorescence co-localization and immunoblotting. Finally, morphological methods such as Micro-CT and HE, TRAP staining and immunological methods such as immunohistochemistry/fluorescence staining were used to assess the mechanisms by which AI-2 regulates periodontitis progression.
AI-2 level was positively correlated with the progression of periodontitis stages and was significantly higher in periodontitis stage III and IV patients. AI-2 promotes macrophage classical polarization and facilitates the secretion of inflammatory factors in vitro, which is dependent on the activation of the NF-κB signaling pathway. AI-2 promotes alveolar bone resorption, but D-ribose acts as a quorum sensing inhibitor to alleviate macrophage classical polarization and attenuates alveolar bone resorption and inflammatory responses in periodontitis mice.
Our study demonstrates that AI-2 promoted classical polarization of macrophage and exacerbated periodontal inflammation which could be reversed by D-ribose.
群体感应信号在牙周炎发展过程中的免疫炎症反应中的作用尚不清楚。本研究旨在探讨群体感应信号分子自诱导物-2（Autoinducer-2，AI-2）对牙周炎免疫微环境中巨噬细胞表型重塑的影响，进一步阐明其机制，并发现抗牙周炎的抑制剂。
采用生物发光实验和牙周炎模型来证明牙周炎进展与AI-2之间的关联。接下来，将AI-2刺激的巨噬细胞用于转录组测序，并结合流式细胞术、qPCR和免疫荧光对免疫图谱进行表征。通过荧光共定位和免疫印迹证实AI-2对NF-κB信号通路的激活。最后，使用Micro-CT和HE等形态学方法、TRAP染色以及免疫组化/荧光染色等免疫学方法来评估AI-2调节牙周炎进展的机制。
AI-2水平与牙周炎分期进展呈正相关，在牙周炎III期和IV期患者中显著更高。AI-2在体外促进巨噬细胞的经典极化并促进炎症因子的分泌，这依赖于NF-κB信号通路的激活。AI-2促进牙槽骨吸收，但D-核糖作为群体感应抑制剂可减轻巨噬细胞的经典极化，并减轻牙周炎小鼠的牙槽骨吸收和炎症反应。
我们的研究表明，AI-2促进巨噬细胞的经典极化并加剧牙周炎症，而D-核糖可逆转这种情况。
