Human β-defensin 3 suppresses Porphyromonas gingivalis lipopolysaccharide-induced inflammation in RAW 264.7 cells and aortas of ApoE-deficient mice.
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.
Department of Periodontology, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, China; Central Laboratory of Stomatology, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, China.
Tianying
T
Bian
Department of Periodontology, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, China; Central Laboratory of Stomatology, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, China.
Lili
L
Li
Department of Periodontology, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, China; Central Laboratory of Stomatology, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, China.
Jinglu
J
Lyu
Department of Periodontology, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, China; Central Laboratory of Stomatology, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, China.
Di
D
Cui
Central Laboratory of Stomatology, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, China; Department of Orthodontics, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, China.
Lang
L
Lei
Department of Periodontology, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, China; Central Laboratory of Stomatology, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, China. Electronic address: fhyan2005@126.com.
Fuhua
F
Yan
D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics; D050197:Atherosclerosis / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy* / Q000382:microbiology; D018932:Chemokine CCL2 / Q000097:blood; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy*; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D015850:Interleukin-6 / Q000235:genetics; D008070:Lipopolysaccharides / Q000737:chemistry / Q000633:toxicity; D051379:Mice; D020929:Mitogen-Activated Protein Kinase Kinases / Q000187:drug effects / Q000235:genetics; D016966:Porphyromonas gingivalis / Q000737:chemistry / Q000472:pathogenicity; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D023083:beta-Defensins / Q000008:administration & dosage* / Q000378:metabolism
D001057:Apolipoproteins E; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; C422950:DEFB103A protein, human; D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D023083:beta-Defensins; D018799:Intercellular Adhesion Molecule-1; D020929:Mitogen-Activated Protein Kinase Kinases
Anti-inflammatory; Atherosclerosis; MAPK pathway; hBD3