Human β-defensin 3 suppresses Porphyromonas gingivalis lipopolysaccharide-induced inflammation in RAW 264.7 cells and aortas of ApoE-deficient mice

• hBD3 inhibits the production of pro-inflammatory cytokines in vivo and in vitro.
• hBD3 attenuates plaque formation induced by P. gingivalis LPS in ApoE−/− mice.
• The anti-inflammatory effect might be related with inhibition of MAPK pathway.

Human beta-defensin 3 (hBD3) is an antimicrobial peptide showing immunomodulatory effect on both innate and acquired immune response. Atherosclerosis is an inflammatory disease characterized by accumulation of lipids in the vascular wall. In this study, we evaluated whether hBD3 could attenuate the atherosclerosis development accelerated by Porphyromonas gingivalis lipopolysaccharide (Pg-LPS) with apolipoprotein E-deficient (ApoE−/−) mice. We observed that, in vivo, hBD3 inhibited serum MCP-1, sICAM-1 levels of ApoE-deficient mice exposed to Pg-LPS in a chronic inflammation model. Serum levels of total cholesterol (TC) and low-density lipoprotein (LDL) were also markedly reduced with hBD3 intervention. In addition, thinned vascular walls, less macrophage infiltration and the formation of atherosclerotic lesions were observed in the hBD3-treated group. Furthermore, in vitro, hBD3 profoundly suppressed the production of TNF-α and IL-6 in RAW 264.7 cells induced by Pg-LPS in a dose-dependent manner. Moreover, hBD3 attenuated the phosphorylation of p38 and ERK1/2 in the mitogen-activated protein kinase (MAPK) pathway. Taken together, our work has revealed that hBD3 exhibits potent anti-inflammatory properties both in vitro and in vivo, and this effect might be correlated with inhibition of MAPK pathway.