Kato S, Muro M, Akifusa S, Hanada N, Semba I, Fujii T, Kowashi Y, Nishihara T
Department of Oral Science, National Institute of Health, Tokyo, Japan.
Infect Immun. 1995 Oct;63(10):3914-9. doi: 10.1128/iai.63.10.3914-3919.1995.
The gram-negative bacterium Actinobacillus actinomycetemcomitans is considered an important etiological agent in periodontal diseases. In this study, we show that A. actinomycetemcomitans strains are cytotoxic for the murine macrophage cell line J774.1. On the other hand, Porphyromonas gingivalis strains, other gram-negative oral species implicated in adult periodontitis, showed weak cytotoxic effects. For this to occur, A. actinomycetemcomitans had to gain entry into the macrophages, since cytotoxicity was prevented by cytochalasin D. We demonstrate that cell death induced by A. actinomycetemcomitans Y4 occurs through apoptosis, as shown by changes in nuclear morphology, an increase in the proportion of fragmented DNA, and the typical ladder pattern of DNA fragmentation indicative of apoptosis. We further sought to determine whether the cytotoxicity induced by A. actinomycetemcomitans Y4 could be modulated by the protein kinase inhibitors H7 and HA1004. Apoptotic cell death induced by A. actinomycetemcomitans Y4 was suppressed by H7 but was relatively unaffected by HA1004. These findings suggest that the signals of protein kinases may regulate apoptosis induced by A. actinomycetemcomitans Y4. The ability of A. actinomycetemcomitans to promote the apoptosis of macrophages may be important for the initiation of infection and the development of periodontal diseases.
革兰氏阴性菌伴放线放线杆菌被认为是牙周疾病的一种重要病原体。在本研究中，我们发现伴放线放线杆菌菌株对小鼠巨噬细胞系J774.1具有细胞毒性。另一方面，牙龈卟啉单胞菌菌株，即另一种与成人牙周炎相关的革兰氏阴性口腔菌，显示出较弱的细胞毒性作用。要产生这种情况，伴放线放线杆菌必须进入巨噬细胞，因为细胞松弛素D可阻止细胞毒性。我们证明，伴放线放线杆菌Y4诱导的细胞死亡是通过凋亡发生的，这表现为核形态的变化、DNA片段化比例的增加以及指示凋亡的典型DNA片段梯形模式。我们进一步试图确定伴放线放线杆菌Y4诱导的细胞毒性是否可被蛋白激酶抑制剂H7和HA1004调节。伴放线放线杆菌Y4诱导的凋亡性细胞死亡被H7抑制，但相对不受HA1004的影响。这些发现表明蛋白激酶信号可能调节伴放线放线杆菌Y4诱导的凋亡。伴放线放线杆菌促进巨噬细胞凋亡的能力可能对感染的起始和牙周疾病的发展很重要。
