Xu Hongyan, Wang Tao, Yang Ying
Department of Stomatology, Shaanxi Provincial People's Hospital, China.
Department of Otorhinolaryngology Head and Neck Surgery, Shaanxi Provincial People's Hospital, China.
Arch Oral Biol. 2025 May;173:106190. doi: 10.1016/j.archoralbio.2025.106190. Epub 2025 Feb 12.
Periodontitis is a chronic inflammatory disease characterized by tissue destruction and oxidative stress, primarily driven by the imbalance of immune responses. Bactericidal/permeability-increasing fold-containing family A member 1 (BPIFA1) has emerged as a key modulator of inflammation and immune homeostasis.
This study investigates the role of BPIFA1 in periodontitis by focusing on its regulatory effects on the NF-κB/IκB signaling pathway and macrophage M1/M2 polarization.
Saliva and periodontal tissue samples were collected from 20 periodontitis patients and 20 healthy volunteers. BPIFA1 expression was analyzed using qRT-PCR and Western blot. In vivo studies were conducted in wild-type and BPIFA1-knockout (KO) mice, where periodontitis was induced via ligature placement and LPS injections. Oxidative stress markers (ROS, MDA, SOD), inflammatory cytokines (TNF-α, IL-6), and macrophage polarization markers (iNOS, CD86, Arg-1, CD206) were quantified. NF-κB pathway activation was assessed through Western blot analysis.
BPIFA1 expression was significantly reduced in periodontitis patients and BPIFA1-KO mice. Loss of BPIFA1 resulted in increased oxidative stress, heightened NF-κB activation, and an imbalance in macrophage polarization, with increased M1 (pro-inflammatory) and decreased M2 (anti-inflammatory) macrophages. Additionally, BPIFA1 deficiency promoted Th17 differentiation and suppressed Treg cells, exacerbating periodontal inflammation.
BPIFA1 plays a critical role in inhibiting periodontitis progression by regulating the NF-κB/IκB signaling pathway and restoring macrophage M1/M2 balance. These findings highlight BPIFA1 as a potential therapeutic target for periodontitis management.
牙周炎是一种以组织破坏和氧化应激为特征的慢性炎症性疾病，主要由免疫反应失衡驱动。含杀菌/通透性增加折叠家族A成员1（BPIFA1）已成为炎症和免疫稳态的关键调节因子。
本研究通过关注BPIFA1对NF-κB/IκB信号通路和巨噬细胞M1/M2极化的调节作用，探讨其在牙周炎中的作用。
收集20例牙周炎患者和20名健康志愿者的唾液和牙周组织样本。采用qRT-PCR和蛋白质免疫印迹法分析BPIFA1表达。在野生型和BPIFA1基因敲除（KO）小鼠中进行体内研究，通过结扎和注射脂多糖诱导牙周炎。对氧化应激标志物（ROS、MDA、SOD）、炎性细胞因子（TNF-α、IL-6）和巨噬细胞极化标志物（iNOS、CD86、Arg-1、CD206）进行定量分析。通过蛋白质免疫印迹分析评估NF-κB通路的激活情况。
牙周炎患者和BPIFA1-KO小鼠中BPIFA1表达显著降低。BPIFA1缺失导致氧化应激增加、NF-κB激活增强以及巨噬细胞极化失衡，促炎M1巨噬细胞增加，抗炎M2巨噬细胞减少。此外，BPIFA1缺乏促进Th17分化并抑制调节性T细胞，加剧牙周炎症。
BPIFA1通过调节NF-κB/IκB信号通路和恢复巨噬细胞M1/M2平衡，在抑制牙周炎进展中起关键作用。这些发现突出了BPIFA1作为牙周炎治疗潜在靶点的作用。
