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.
Keywords: Autophagy; GYY4137; H(2)S; Inflammation; Periodontal ligament cells; Periodontitis.
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