Hydrogen sulfide exacerbated periodontal inflammation and induced autophagy in experimental periodontitis

Hydrogen sulfide (H₂S), 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 H₂S participates in pathogenesis and whether H₂S induces Autophagy in periodontitis remain partially unknown. In this article, we determined the role of the slow-releasing H₂S 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.