BPIFA1 inhibits periodontitis by regulating the NF-κB/IκB signaling pathway and macrophage M1/M2 polarization

Abstract

Background

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.

Objectives

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.

Methods

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.

Results

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.

Conclusion

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.