Expression of NOD2 is increased in inflamed human dental pulps and lipoteichoic acid-stimulated odontoblast-like cells
Expression of NOD2 is increased in inflamed human dental pulps and lipoteichoic acid-stimulated odontoblast-like cells
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DOI：
10.1177/1753425909348527
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发表时间：
2011-02-01
期刊：
影响因子：
3.2
通讯作者：
Farges, Jean-Christophe
中科院分区：
文献类型：
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作者：
Keller, Jean-Francois;Carrouel, Florence;Farges, Jean-Christophe
人类成牙本质细胞会触发对龋齿过程中侵入牙齿组织的口腔细菌的免疫反应。到目前为止，他们的能力，以调节表达的核苷酸结合结构域富含亮氨酸的重复含有受体NOD2时，革兰氏阳性菌的挑战是未知的。在这项研究中，我们研究了NOD2的表达在健康和发炎的人牙髓细菌的挑战，并在培养的成牙本质细胞样细胞刺激脂磷壁酸（LTA），Toll样受体（TLR）2激动剂，这是特定的革兰氏阳性菌。我们发现，NOD2基因的表达显着上调牙髓急性炎症相比，健康的。在体外培养条件下，LTA可促进成牙本质细胞样细胞NOD2基因表达和蛋白水平的提高。与牙髓成纤维细胞相比，成牙本质细胞样细胞的增加更明显。用抗TLR2抗体在成牙本质细胞样细胞中进行的阻断实验强烈降低了NOD2基因表达的增加，而用合成的TLR2配体Pam（2）CSK（4）刺激证实了TLR2参与后NOD2基因的上调。这些数据表明，NOD2的上调是成牙本质细胞对革兰氏阳性菌的免疫反应的一部分，并可能在保护人类牙髓免受致龋病原体的有害影响方面发挥重要作用。
Human odontoblasts trigger immune response s to oral bacteria that invade dental tissues during the caries process. To date, their ability to regulate the expression of the nucleotide-binding domain leucine-rich repeat containing receptor NOD2 when challenged by Gram-positive bacteria is unknown. In this study, we investigated NOD2 expression in healthy and inflamed human dental pulps challenged by bacteria, and in cultured odontoblast-like cells stimulated with lipoteichoic acid (LTA), a Toll-like receptor (TLR) 2 agonist which is specific for Gram-positive bacteria. We found that NOD2 gene expression was significantly up-regulated in pulps with acute inflammation compared to healthy ones. In vitro, LTA augmented NOD2 gene expression and protein level in odontoblast-like cells. The increase was more pronounced in odontoblast-like cells compared to dental pulp fibroblasts. Blocking experiments in odontoblast-like cells with anti-TLR2 antibody strongly reduced the NOD2 gene expression increase, whereas stimulation with the synthetic TLR2 ligand Pam(2)CSK(4) confirmed NOD2 gene up-regulation following TLR2 engagement. These data suggest that NOD2 up-regulation is part of the odontoblast immune response to Gram-positive bacteria and might be important in protecting human dental pulp from the deleterious effects of cariogenic pathogens.