Modulation of LPS-associated virulence activity for reduction of periodontal inflammatory burden

TL;DR

This study shows that reducing LPS activity in oral biofilms using LL-37 and Polymyxin B can significantly lower inflammation in periodontal diseases.

Contribution

The study introduces LL-37 and Polymyxin B as novel modulators of LPS virulence activity in periodontal biofilms.

Findings

LL-37 and Polymyxin B reduced endotoxin activity by over 90% in saliva and subgingival biofilms.

Modulation suppressed pro-inflammatory cytokines by 40–75% without affecting anti-inflammatory cytokines.

LL-37 and Polymyxin B showed complementary effects on NF-κB and IRF signaling pathways.

Abstract

Dysbiotic oral biofilms produce virulence factors, such as lipopolysaccharide (LPS), triggering and sustaining chronic inflammation in periodontal tissues. Modulation of the bioactivity of these products offers a potential novel, adjunctive approach beyond conventional periodontal therapy.

Pooled saliva and subgingival biofilm samples from 324 healthy, gingivitis, and periodontitis participants were assessed for endotoxin activity using the recombinant Factor C (rFC) assay. Functional immune-stimulation was evaluated in THP-1 and THP-1 Dual cell models through NF-κB and IRF pathways activation assessment and cytokine profiling. The modulatory effects of antimicrobial peptide LL-37 and the LPS-binding compound Polymyxin B on saliva and subgingival biofilm inflammatory potential were assessed in the same models.

Recombinant Factor C assays demonstrated marked reductions in endotoxin activity of saliva and subgingival biofilms treated with LL-37 and Polymyxin B (>90% reduction). Both NF-κB and IRF signaling were broadly attenuated following modulation, with polymyxin B exerting greater suppression of NF-κB activity, while LL-37 showed stronger inhibition of IRF, particularly in salivary samples. Pro-inflammatory cytokines secretion by THP-1 cells (IL-1β, IL-6, IL-8, and TNF-α) challenged with bio-modulated samples decreased by 40–75% compared to untreated samples. Interestingly, anti-inflammatory cytokines such as TGF-β and IL-10 remained largely unchanged, suggesting selective suppression of the cytokine cascade.

Modulating LPS-associated virulence activity substantially reduces the inflammatory potential of saliva and subgingival plaque. LL-37 and Polymyxin B illustrate complementary strategies for LPS modulations and highlight the feasibility of their use as adjunctive approaches for the prevention and treatment of periodontal diseases.

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