Department of Orthodontics, School of Stomatology, Tongji University, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, 399 Middle Yanchang Road, Shanghai 200072, China.
Department of Orthodontics, School of Stomatology, Tongji University, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, 399 Middle Yanchang Road, Shanghai 200072, China.
Int Immunopharmacol. 2021 Apr;93:107399. doi: 10.1016/j.intimp.2021.107399. Epub 2021 Jan 30.
Hydrogen sulfide (HS), the metabolite produced by gram-negative bacteria, is present in deep periodontal pockets of periodontitis patients at high concentrations. The harsh conditions in the diseased periodontium may stimulate a local autophagy response. However, how HS participates in pathogenesis and whether HS induces autophagy in periodontitis remain partially unknown. In this article, we determined the role of the slow-releasing HS donor GYY4137 in experimental periodontitis and its possible regulation in autophagy involved. We found that GYY4137 dose-dependently decreased cell viability and increased the level of proinflammatory cytokines in LPS-stimulated human periodontal ligament cells (HPDLCs). Topically applied GYY4137 also exacerbated periodontal inflammation and alveolar bone loss in ligature-induced rats. Moreover, GYY4137 activated autophagy by upregulating the expression levels of the autophagy-related proteins LC3 and Beclin-1 and downregulating P62 in LPS-treated HPDLCs and inflamed periodontal tissues. Blocking autophagy with 3-methyladenine resulted in further increased expression of proinflammatory cytokines in LPS- and GYY4137-induced HPDLCs. Our results indicate that GYY4137 exerted proinflammatory effects and promoted autophagy in periodontitis, and the induced autophagy may function as a cytoprotective mechanism to prevent excessive inflammation.
硫化氢（HS）是革兰氏阴性菌产生的代谢产物，在牙周炎患者深牙周袋中以高浓度存在。患病牙周组织中的恶劣条件可能会刺激局部自噬反应。然而，HS 如何参与发病机制以及 HS 是否会诱导牙周炎中的自噬仍然部分未知。在本文中，我们确定了缓释 HS 供体 GYY4137 在实验性牙周炎中的作用及其在自噬参与中的可能调节作用。我们发现 GYY4137 剂量依赖性地降低细胞活力并增加 LPS 刺激的人牙周韧带细胞（HPDLC）中促炎细胞因子的水平。局部应用 GYY4137 也加重了结扎诱导的大鼠牙周炎的炎症和牙槽骨丢失。此外，GYY4137 通过上调自噬相关蛋白 LC3 和 Beclin-1 的表达水平并下调 LPS 处理的 HPDLC 和炎症牙周组织中 P62 的表达水平来激活自噬。用 3-甲基腺嘌呤阻断自噬会导致 LPS 和 GYY4137 诱导的 HPDLC 中促炎细胞因子的表达进一步增加。我们的结果表明，GYY4137 在牙周炎中发挥促炎作用并促进自噬，诱导的自噬可能作为一种细胞保护机制来防止过度炎症。
