Dental Department, Hejian Hospital of Traditional Chinese Medicine, Cangzhou Central Hospital Medical Group, Cangzhou, Hebei, China.
Dental Clinics, Cangzhou Central Hospital, Cangzhou, Hebei, China.
Immun Inflamm Dis. 2023 Aug;11(8):e959. doi: 10.1002/iid3.959.
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.
多硫化物被报道参与各种重要的生物过程。含有 2 个硫氢基的 N-乙酰-L-半胱氨酸多硫化物（NAC-S2）调节多种 Toll 样受体（TLR）信号通路。在这里，我们旨在确定 NAC-S2 在牙周炎中的作用，并探讨其潜在机制。
通过结扎野生型、TLR4 和 Myd88 小鼠第一和第二磨牙之间的龈下组织建立牙周炎小鼠模型。
NAC-S2 不影响骨髓中巨噬细胞（CD11b F4/80）或中性粒细胞（CD11b GR-1）的比例。在机制上，NAC-S2 可抑制脂多糖（LPS）、酵母聚糖 A 或聚 I:C 诱导的骨髓来源巨噬细胞（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 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激活激酶 1（TAK1）的磷酸化水平不受 NAC-S2 的影响。在野生型牙周炎小鼠中，NAC-S2 给药可减少牙釉质-牙骨质结合部-牙槽骨嵴（CEJ-ABC）距离和 TNF、IL-6 和 IL-1β的相对 mRNA 表达，而在 TLR4 缺陷或 Myd88 缺陷小鼠中则观察不到这种现象。
这些结果表明，NAC-S2 可改善 TLR4/NF-κB 通路介导的小鼠牙周炎模型中的炎症。
