Effects Of Human β-defensin 3 On Acute Inflammation Induced By Porphyromonas Gingivalis Lipopolysaccharide

[Objective]To investigate the effect of human β-defensin 3 (hBD3) on acute inflammation induced by Porphyromonas gingivalis lipopolysaccharide (P.g-LPS) and reveal its anti-inflammatory mechanism, which may provide research foundation for the medication of systemic inflammatory diseases associated with periodontal infection.[Methods]Firstly, mice and murine macrophages were stimulated with P.g-LPS in order to establish acute inflammation models. The productions and mRNA expression levels of proinflammatory mediators in sera and culture supernatants or in cells were measured using ELISA or Q-PCR. The activity of NF-κB signaling pathway was evaluated by detecting the phosphorylation level of p65 subunit using Western Blot. The role of macrophage during acute inflammation was confirmed by analyzing the expressions of proinflammatory cytokines in vivo and in vitro. Then, the effect of hBD3 on acute inflammation induced by P.g-LPS was investigated by evaluating the inhibition of proinflammatory mediators expression in sera and culture supernatants using ELISA and nitrate reductase assay. The suppressive effect of hBD3 on NF-κB signaling pathway activation was evaluated by detecting the phosphorylated p65 subunit (p-p65) using Western Blot. Finally, murine macrophages were treated with P.g-LPS alone, hBD3 alone or both together. The promotions of P.g-LPS and hBD3 in macrophage polarization were evaluated by detecting the signature molecular mRNA level of M1 or M2 macrophage using Q-PCR.[Results]1. P.g-LPS could initiate the immuno-reaction in macrophages via activating NF-κB signaling pathway, which would lead to the accumulation of proinflammatory mediators and the onset of acute inflammation in experimental mice.2. hBD3 could alleviate the inflammatory response of macrophages by inhibiting the activation of proinflammatory signaling pathway induced by.Pg-LPS together with polarize macrophages into anti-inflammatory M2 phenotype, which contributed to the anti-inflammatory effect of hBD3 in vivo.[Conclusion]hBD3 could down-regulate the inflammatory responses associated with P.g-LPS in macrophages and played an anti-inflammatory role in vivo. The potential application of hBD3 in prevention and treatment of systemic inflammatory diseases associated with periodontal infection is brilliant.