β-defensin 3 modulates macrophage activation and orientation during acute inflammatory response to Porphyromonas gingivalis lipopolysaccharide

Cytokine. 2017 Apr:92:48-54. doi: 10.1016/j.cyto.2016.12.015. Epub 2017 Jan 13.

Abstract

β-defensin 3, a multifunctional antimicrobial peptide, has immuno-regulatory activities. We investigated the modulatory mechanism of human β-defensin 3 (hBD3) on acute inflammatory response resulted from Porphyromonas gingivalis lipopolysaccharide (P.g-LPS), which plays a pro-inflammatory role in periodontal infection and its derived systemic inflammation. P.g-LPS was administrated to mice and murine macrophages alone or along with hBD3. P.g-LPS could lead to acute inflammation as soon as 2h. And it was observed that hBD3 significantly decreased the production of pro-inflammatory biomarkers of in response to P.g-LPS in vivo and in vitro in the early stage. Interestingly, although hBD3 as well as P.g-LPS stimulated the expression of TLR2 mRNA in macrophages in this study, hBD3 exhibited suppressive effect on the downstream NF-κB signaling pathway activated by P.g-LPS. And above all, hBD3 could polarize macrophages into M2 phenotype and this contributed to its anti-inflammatory property. These results indicated that hBD3 could have therapeutic effect on systemic inflammation associated with periodontal infections via modulating macrophage activation and orientation.

Keywords: Immuno-regulatory; Macrophage orientation; P.g-LPS; β-defensin 3.

MeSH terms

  • Acute Disease
  • Animals
  • Humans
  • Inflammation / chemically induced
  • Inflammation / genetics
  • Inflammation / immunology
  • Lipopolysaccharides / chemistry
  • Lipopolysaccharides / toxicity*
  • Macrophage Activation / drug effects*
  • Macrophage Activation / genetics
  • Macrophages / immunology*
  • Male
  • Mice
  • Mice, Knockout
  • NF-kappa B / genetics
  • NF-kappa B / immunology
  • Porphyromonas gingivalis / chemistry*
  • Signal Transduction / drug effects*
  • Signal Transduction / genetics
  • Signal Transduction / immunology
  • beta-Defensins / pharmacology*

Substances

  • DEFB103A protein, human
  • Lipopolysaccharides
  • NF-kappa B
  • beta-Defensins