Human (β-defensin 3 suppresses Porphyromonas gingivalis lipopolysaccharide-induced inflammation in RAW 264.7 cells and aortas of ApoE-deficient mice
Human (β-defensin 3 suppresses Porphyromonas gingivalis lipopolysaccharide-induced inflammation in RAW 264.7 cells and aortas of ApoE-deficient mice
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人β-防御素 3 抑制 ApoE 缺陷小鼠的 RAW 264.7 细胞和主动脉中牙龈卟啉单胞菌脂多糖诱导的炎症
DOI：
10.1016/j.peptides.2016.06.002
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发表时间：
2016-08-01
期刊：
影响因子：
3
通讯作者：
Yan, Fuhua
中科院分区：
文献类型：
--
作者：
Bian, Tianying;Li, Lili;Yan, Fuhua
人β-防御素 3 (hBD3) 是一种抗菌肽，对先天性和获得性免疫反应均具有免疫调节作用。动脉粥样硬化是一种以血管壁脂质积聚为特征的炎症性疾病。在这项研究中，我们利用载脂蛋白 E 缺陷 (ApoE-/-) 小鼠评估了 hBD3 是否可以减轻牙龈卟啉单胞菌脂多糖 (Pg-LPS) 加速的动脉粥样硬化发展。我们观察到，在慢性炎症模型中，hBD3 抑制暴露于 Pg-LPS 的 ApoE 缺陷小鼠的血清 MCP-1、sICAM-1 水平。 hBD3 干预也显着降低了血清总胆固醇 (TC) 和低密度脂蛋白 (LDL) 水平。此外，在hBD3治疗组中观察到血管壁变薄、巨噬细胞浸润减少以及动脉粥样硬化病变的形成。此外，在体外，hBD3 显着抑制 TNF-α 的产生。 Pg-LPS 以剂量依赖性方式诱导 RAW 264.7 细胞中的 IL-6 和 IL-6。此外，hBD3 减弱了丝裂原激活蛋白激酶 (MAPK) 途径中 p38 和 ERK112 的磷酸化。综上所述，我们的工作表明 hBD3 在体外和体内均表现出有效的抗炎特性，这种作用可能与 MAPK 通路的抑制有关。 (C) 2016 Elsevier Inc. 保留所有权利。
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-alpha. 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 ERK112 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. (C) 2016 Elsevier Inc. All rights reserved.