报道了多硫化物参与了各种重要的生物过程。具有2个硫氧指团的N-乙酰-L-半胱氨酸多硫化物（NAC-S2）调节了多样的类似受体（TLR）信号通路。本研究旨在确定NAC-S2在牙周炎中的作用并探索潜在机制。采用在野生型、TLR4-/- 和 Myd88-/-小鼠之间的第一和第二磨牙之间结扎的方法建立牙周炎小鼠模型。NAC-S2不会影响骨髓中巨噬细胞（CD11b+ F4/80+）或中性粒细胞（CD11b+ GR-1+ ）的比例。从机械上来说，脂多糖（LPS）、酵母蛋白A（Zymosan A）或聚I: C可诱导NAC-S2抑制骨髓源性巨噬细胞（BMDMs）中肿瘤坏死因子（TNF）、白细胞介素（IL）-6和IL-1β的表达。另一方面，NAC-S2抑制了LPS诱导的BMDMs中IκB-α、p65和IκB激酶（IKK）-β的磷酸化水平，而LPS诱导的ERK1/2、p38和转化生长因子β激活的激酶1（TAK1）的磷酸化不能被NAC-S2影响。在野生型牙周炎小鼠中，NAC-S2处理降低了牙颈釉质-牙槽骨峰（CEJ-ABC）距离以及TNF、IL-6和IL-1β相关mRNA的相对表达，而在TLR4缺陷或Myd88缺陷小鼠中无法观察到这种现象。所有这些结果表明，NAC-S2可以改善TLR4/NF-κB途径介导的小鼠牙周炎模型中的炎症。© 2023 The Authors. Immunity, inflammation and disease出版自John Wiley & Sons Ltd.

Polysulfides are reported to be involved in various important biological processes. N-acetyl-l-cysteine polysulfide with 2 sulfane sulfur atoms (NAC-S2) regulates diverse toll-like receptor (TLR) signaling pathways. Here, we aimed to determine the role of NAC-S2 in periodontitis and explore the potential mechanism.A periodontitis mouse model was established by ligating the subgingival between the first and second molars in wild-type, TLR4-/- , and Myd88-/- mice.NAC-S2 did not affect the proportion of macrophages (CD11b+ F4/80+ ) or neutrophils (CD11b+ GR-1+ ) in the bone marrow. Mechanically, lipopolysaccharides (LPS), Zymosan A, or poly I: C induced tumor necrosis factor (TNF), interleukin (IL)-6, and IL-1β expression in bone marrow-derived macrophages (BMDMs) could be inhibited by NAC-S2. On the other hand, NAC-S2 suppressed the phosphorylation levels of IκB-α, p65, and IκB kinase (IKK)-β induced by LPS in BMDMs, while LPS induced phosphorylation of ERK1/2, p38, and transforming growth factor β-activated kinase 1 (TAK1) could not be affected by NAC-S2. In wild-type periodontitis mice, NAC-S2 administration decreased the cemento-enamel-junction-alveolar bone crest (CEJ-ABC) distance and the relative mRNA expression of TNF, IL-6, and IL-1β, while such phenomena could not be observed in TLR4 deficiency or Myd88 deficiency mice.All of these results indicate that NAC-S2 ameliorates TLR4/NF-κB pathway mediated inflammation in mouse periodontitis model.© 2023 The Authors. Immunity, Inflammation and Disease published by John Wiley & Sons Ltd.