Development of prevention method of periodontal diseases by understanding the mechanisms of intracellular invasion by periodontopathic bacteria

伴放线放线杆菌（Actinobacillusactinomycetemcomitans）是一种革兰氏阴性、嗜二氧化碳球杆菌，其被认为是特别是在严重形式的青少年和成人牙周炎中的病原体。既往研究表明伴放线菌可以侵入进展期牙周炎的牙周组织，并在宿主细胞内存活。我们以前的研究表明，海洋巨噬细胞样细胞系的凋亡细胞死亡是由A。伴放线菌感染在此凋亡过程中，观察到几个半胱天冬酶的激活。在普通医学中，有报道说，一些重要的病原菌可以在宿主细胞内感染和繁殖，引起严重的危及生命的感染。本文详细分析了一些病原菌的细胞内侵袭机制，并报道了几种半胱氨酸蛋白酶在侵袭过程中的激活。我们假设导致军团病的嗜肺军团菌 ...更多信息 酶和牙周病细菌伴放线菌可能以类似的方式侵入宿主细胞内，因为两者都靶向巨噬细胞侵入并激活宿主细胞中类似的半胱天冬酶组。我们首先采用了为A.放线菌属（actinomycetemcomitans）与L.嗜肺菌小鼠巨噬细胞系J744.1和小鼠单核细胞系RAW 264.7均显示通过这些细菌的感染诱导细胞死亡。然而，L.嗜肺菌在细胞爆炸前细胞内容物中充满了大量的细菌细胞而坏死。不同细菌引起的细胞死亡的差异可能取决于不同的信号通路，即使激活了相似的半胱氨酸蛋白酶。表达抗凋亡基因Bcl-2或Bcl-x_L的RAW264.7细胞不能被A.伴放线菌因此，对A.放线菌共生菌是独特的，我们需要进一步分析这些机制，以预防牙周疾病。少

Actinobacillus actinomycetemcomitans is a Gram-negative, capnophilic coccobacillus which has been considered to be an etiologic agent especially in the severe form of juvenile and adult periodontitis. Previous studies suggested that A.actinomycetemcomitans can invade into periodontal tissues of advanced periodontitis and then survive inside the host cells. We previously showed that apoptotic cell death of the marine macrophage-like cell line was induced by A. actinomycetemcomitans infection. During the course of this apoptosis, activation of several caspases was observed. In general medicine, the facts that severl important pathogenic bacteria can infect and multiple inside the host cells and cause the severe life-threaten infection has been reported. Intracellular invasion mechanisms of some pathogenic bacteria were analyzed in detail, and several caspases has been reported to activate during the course of invasion. We hypothesized that Legionella pneumophila, which causes legion dise … More ase, and periodontopathic bacteria, A.actinomycetemcomitans, might invade inside the host cells in similar manner, because both target macrophaees to invade and activate similar set of caspases in host cells. We first adapted the invasion assay designed for A. actinomycetemcomitans to that for L. pneumphila. Mouse macrophage cell line J744.1 and mouse monocyte cell line RAW264.7 are both showed to induce cell death by infection of these bacteria. However, the cell death cased by L. pneumophila was necrosis because the content of cell is filled with multipled bacterial cells just before cell explosion. The difference of the cell death caused by each bacterium might depended on the different signal pathway which are activated by infection even if the similar set of caspases was activated. The RAW264.7 cells which constitutively expressed anti-apopotic Bcl-2 or Bcl-x_L did not rescue cell death by the infection of A. actinomycetemcomitans. Considering all, the mechanisms of invasion and infection of A. actinomycetemcomitans is unique and we need further analysis of these mechanisms for preventing periodontal diseases. Less