Cell cycle arrest of human gingival fibroblasts and periodontal ligament cells by Actinobacillus actinomycetemcomitans:: involvement of the cytolethal distending toxin
Cell cycle arrest of human gingival fibroblasts and periodontal ligament cells by Actinobacillus actinomycetemcomitans:: involvement of the cytolethal distending toxin
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DOI：
10.1111/j.1600-0463.2004.apm1121006.x
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发表时间：
2004-10-01
期刊：
影响因子：
2.8
通讯作者：
Johansson, A
中科院分区：
文献类型：
--
作者：
Belibasakis, GN;Mattsson, A;Johansson, A
细胞致死性膨胀毒素（Cdt）是由几种革兰氏阴性细菌产生的，可导致哺乳动物细胞生长停滞和形态学改变。伴放线放线杆菌参与局部侵袭性牙周炎的发病机制，也产生影响牙周结缔组织细胞的Cdt。本研究的目的是研究这些细胞在细胞周期的哪个阶段被A.放线菌共生菌，并评估其Cdt的参与。人牙龈成纤维细胞和牙周膜细胞用A.放线菌共生菌提取物或纯化的Cdt，并通过碘化丙啶染色和流式细胞术进行细胞周期分析。细胞暴露于A.放线菌共生野生型菌株，或纯化的Cdt，被阻滞在G1和G2/M期，并出现扩大相比，相应的对照。G1期和G2/M期阻滞细胞均出现细胞增大。相比之下，暴露于A.伴放线菌CDT基因敲除突变株的细胞周期时相分布和大小与对照相似。总之，A.伴随放线菌引起牙周结缔组织细胞G1期和G2/M期生长停滞和增大，这归因于其Cdt。
The cytolethal distending toxin (Cdt) is produced by several Gram-negative bacterial species and causes growth arrest and morphological alterations in mammalian cells. Actinobacillus actinomycetemcomitans, which is involved in the pathogenesis of localized aggressive periodontitis, also produces a Cdt that affects periodontal connective tissue cells. The aim of this study was to investigate in which phase of the cell cycle these cells are arrested and enlarged when challenged with A. actinomycetemcomitans, and to evaluate the involvement of its Cdt. Human gingival fibroblasts and periodontal ligament cells were challenged with A. actinomycetemcomitans extract, or with purified Cdt, and cell cycle analysis was performed by propidium iodide staining and flow cytometry. Cells exposed to an A. actinomycetemcomitans wild-type strain, or to purified Cdt, were arrested in both G1 and G2/M phases, and appeared enlarged compared to the corresponding controls. The cellular enlargement occurred in both G1 and G2/M arrested cells. In contrast, cells exposed to an A. actinomycetemcomitans cdt-knockout mutant strain showed cell cycle phase distribution and size similar to the controls. In conclusion, A. actinomycetemcomitans causes a combined G1 and G2/M growth arrest and enlargement in periodontal connective tissue cells, which is attributed to its Cdt.