Sato Sunao, Kitagawa Masae, Sakamoto Kiyako, Iizuka Shinji, Kudo Yasusei, Ogawa Ikuko, Miyauchi Mutsumi, Chu Emily Y, Foster Brian L, Somerman Martha J, Takata Takashi
Department of Oral and Maxillofacial Pathobiology, Division of Frontier Medical Science, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, Japan.
J Periodontol. 2008 Mar;79(3):535-40. doi: 10.1902/jop.2008.070311.
Enamel matrix derivative (EMD) is used clinically to promote periodontal tissue regeneration with variable efficacy. EMD application results in significantly higher frequencies of sites without clinical signs of inflammation; additionally, patients receiving EMD therapy report significantly less post-treatment discomfort. However, there are few reports that focus on defining the biologic mechanisms for the observed anti-inflammatory effects of EMD. The aim of this study was to evaluate the influence of EMD on inflammatory-associated markers using an in vitro monocyte assay.
Rat monocytes were exposed to lipopolysaccharide (LPS; 100 ng/ml from Escherichia coli or Actinobacillus actinomycetemcomitans) along with EMD (0, 50, 100, or 200 microg/ml). Levels of tumor necrosis factor-alpha (TNF-alpha) and prostaglandin E(2) (PGE(2)) in conditioned media were analyzed by enzyme-linked immunosorbent assay. In addition, the effects of exogenous PGE(2) on TNF-alpha production from LPS-stimulated monocytes were determined.
LPS-stimulated monocytes exposed to EMD exhibited a decrease in TNF-alpha production (0.10- to 0.52-fold) and an increase in PGE(2) production (1.31- to 2.71-fold) compared to controls not treated with EMD. Exogenously applied PGE(2) decreased TNF-alpha production by LPS-stimulated monocytes in a dose-dependent manner, and EMD treatment enhanced this PGE(2)-mediated inhibition of TNF-alpha production.
In addition to EMD's published role in inducing proliferation, migration, adhesion, mineralization, and differentiation of periodontal ligament cells, our results indicated that EMD modulates two inflammation-associated factors, TNF-alpha and PGE(2), in monocytes.
釉基质衍生物（EMD）在临床上用于促进牙周组织再生，但其疗效各异。应用EMD后，无临床炎症迹象的部位出现频率显著更高；此外，接受EMD治疗的患者报告治疗后不适明显减轻。然而，很少有报告专注于确定EMD所观察到的抗炎作用的生物学机制。本研究的目的是使用体外单核细胞试验评估EMD对炎症相关标志物的影响。
将大鼠单核细胞暴露于脂多糖（LPS；来自大肠杆菌或伴放线放线杆菌的100 ng/ml）以及EMD（0、50、100或200 μg/ml）。通过酶联免疫吸附测定法分析条件培养基中肿瘤坏死因子-α（TNF-α）和前列腺素E2（PGE2）的水平。此外，还确定了外源性PGE2对LPS刺激的单核细胞产生TNF-α的影响。
与未用EMD处理的对照组相比，暴露于EMD的LPS刺激的单核细胞TNF-α产生减少（0.10至0.52倍），PGE2产生增加（1.31至2.71倍）。外源性应用的PGE2以剂量依赖性方式降低LPS刺激的单核细胞产生的TNF-α，并且EMD处理增强了这种PGE2介导的对TNF-α产生的抑制作用。
除了EMD在诱导牙周膜细胞增殖、迁移、黏附、矿化和分化方面已公布的作用外，我们的结果表明EMD可调节单核细胞中两种炎症相关因子TNF-α和PGE2。
