PDF(Pubmed)
Abstract：
(1) Background: Peptides are appealing as pharmacological materials because they are easily produced, safe, and tolerable. Despite increasing gum-care awareness, periodontitis is still prevalent and is influenced by factors like high sugar consumption, smoking, and aging. Porphyromonas gingivalis is considered a major etiologic agent of periodontitis and activates the NLR family pyrin domain containing 3 (NLRP3) but is absent in melanoma 2 (AIM2) inflammasomes, resulting in pro-inflammatory cytokine release. (2) Methods: We examined the anti-inflammatory effects of 18 peptides derived from human stromal cell-derived factor-1 (SDF-1) on THP-1 macrophages. Inflammation was induced by P. gingivalis, and the anti-inflammatory effects were analyzed using molecular biological techniques. In a mouse periodontitis model, alveolar bone resorption was assessed using micro-CT. (3) Results: Of the 18 SDF-1-derived peptides, S10 notably reduced IL-1β and TNF-α secretion. S10 also diminished the P. gingivalis-induced expression of NLRP3, AIM2, ASC (apoptosis-associated speck-like protein), caspase-1, and IL-1β. Furthermore, S10 attenuated the enhanced TLR (toll-like receptor) signaling pathway and decreased the phosphorylation of nuclear factor-κB (NF-κB) and mitogen-activated protein kinases (MAPKs). In addition, S10 mitigated alveolar bone loss in our P. gingivalis-induced mouse model of periodontitis. (4) Conclusions: S10 suppressed TLR/NF-κB/NLRP3 inflammasome signaling and the AIM2 inflammasome in our P. gingivalis-induced murine periodontitis model, which suggests that it has potential use as a therapeutic treatment for periodontitis.
摘要：
(1)背景：肽作为药理材料很有吸引力，因为它们容易产生，安全,和可容忍的。尽管提高了牙龈护理意识，牙周炎仍然很普遍，受到高糖消耗等因素的影响，吸烟,和衰老。牙龈卟啉单胞菌被认为是牙周炎的主要病因，并激活含有NLR家族pyrin结构域3（NLRP3），但在黑色素瘤2（AIM2）炎性体中不存在，导致促炎细胞因子释放。(2)方法:我们检测了18种人基质细胞衍生因子-1(SDF-1)肽对THP-1巨噬细胞的抗炎作用。牙龈卟啉单胞菌诱导炎症，并使用分子生物学技术分析抗炎作用。在小鼠牙周炎模型中，使用Micro-CT评估牙槽骨吸收。(3)结果:18个SDF-1衍生肽,S10显著减少IL-1β和TNF-α分泌。S10还减少了牙龈卟啉单胞菌诱导的NLRP3，AIM2，ASC（凋亡相关斑点样蛋白）的表达，caspase-1和IL-1β。此外，S10减弱了增强的TLR（toll样受体）信号通路，并降低了核因子-κB（NF-κB）和丝裂原活化蛋白激酶（MAPK）的磷酸化。此外,在我们的牙龈卟啉单胞菌诱导的牙周炎小鼠模型中，S10减轻了牙槽骨丢失。(4)结论:在牙龈卟啉单胞菌诱导的小鼠牙周炎模型中,S10抑制TLR/NF-κB/NLRP3炎症小体信号和AIM2炎症小体,这表明它具有作为牙周炎治疗的潜在用途。
