Baik Jung Eun, Ryu Young Hee, Han Ji Young, Im Jintaek, Kum Kee-Yeon, Yun Cheol-Heui, Lee Kangseok, Han Seung Hyun
Department of Oral Microbiology & Immunology, Dental Research Institute and BK21 Program, School of Dentistry, Seoul National University, Seoul, Republic of Korea.
J Endod. 2008 Aug;34(8):975-82. doi: 10.1016/j.joen.2008.05.005. Epub 2008 Jun 20.
Enterococcus faecalis, a pathogenic gram-positive bacterium, is closely related to refractory apical periodontitis. Because lipoteichoic acid (LTA) is considered a major virulence factor of gram-positive bacteria, in the present study, highly pure LTA from E. faecalis was prepared, and its ability to stimulate murine macrophages was investigated in comparison with those of the killed whole cells. Upon exposure to E. faecalis LTA, RAW 264.7 (a murine macrophage cell line) produced a significantly (p < 0.05) high level of tumor necrosis factor-alpha (TNF-alpha) and nitric oxide (NO) in a concentration-dependent manner. It is to note that the LTA was able to stimulate Toll-like receptor 2 (TLR2) but not TLR4. Concomitantly, LTA enhanced the DNA-binding activity of a transcription factor, nuclear factor-kappa B (NF-kappaB), which plays an important role in the transcriptional activation of genes encoding inflammatory mediators. In contrast, heat-killed E. faecalis stimulated both TLR2 and TLR4, whereas the killed E. faecalis whole cells induced significant (p < 0.05) levels of TNF-alpha and NO in RAW 264.7 cells as their LTA did. These results suggest that LTA partially contributes to E. faecalis-induced inflammatory responses.
粪肠球菌是一种致病性革兰氏阳性菌，与难治性根尖周炎密切相关。由于脂磷壁酸（LTA）被认为是革兰氏阳性菌的主要毒力因子，因此在本研究中，制备了来自粪肠球菌的高纯度LTA，并与灭活的全菌进行比较，研究其刺激小鼠巨噬细胞的能力。RAW 264.7（一种小鼠巨噬细胞系）暴露于粪肠球菌LTA后，以浓度依赖的方式产生了显著（p<0.05）高水平的肿瘤坏死因子-α（TNF-α）和一氧化氮（NO）。值得注意的是，LTA能够刺激Toll样受体2（TLR2），但不能刺激TLR4。同时，LTA增强了转录因子核因子-κB（NF-κB）的DNA结合活性，NF-κB在编码炎症介质的基因的转录激活中起重要作用。相比之下，热灭活的粪肠球菌刺激TLR2和TLR4，而灭活的粪肠球菌全菌在RAW 264.7细胞中诱导出与LTA相当的显著（p<0.05）水平的TNF-α和NO。这些结果表明，LTA部分促成了粪肠球菌诱导的炎症反应。
