Porphyromonas gingivalis degrades integrin β1 and induces AIF-mediated apoptosis of epithelial cells
Porphyromonas gingivalis degrades integrin β1 and induces AIF-mediated apoptosis of epithelial cells
复制标题
牙龈卟啉单胞菌降解整合素β1并诱导AIF介导的上皮细胞凋亡
DOI：
10.1080/23744235.2019.1653490
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发表时间：
2019-08-13
影响因子：
5.8
通讯作者：
Pan, Yaping
中科院分区：
文献类型：
--
作者：
Li, Qian;Zhou, Jie;Pan, Yaping
背景资料：牙龈卟啉单胞菌是慢性牙周炎的主要致病菌，它通过菌毛与整合素的相互作用粘附并侵入上皮细胞。牙龈卟啉单胞菌增殖和感染可能影响细胞的存活。在这项研究中，我们进一步研究了介导牙龈卟啉单胞菌诱导的上皮细胞死亡的替代信号通路和细胞粘附分子整合素的作用。方法：采用Annexin V-碘化丙啶（PI）染色法观察牙龈卟啉单胞菌对人口腔上皮KB细胞的作用。JC-1染色测定线粒体膜电位（MMP）。采用实时定量PCR和Western blot检测细胞中整合素β 1、凋亡诱导因子（AIF）和caspase-3的mRNA和蛋白表达。分光光度法测定Caspase-3活性。结果：牙龈卟啉单胞菌感染下调整合素β 1，并导致细胞脱落，呈剂量和时间依赖性。大量牙龈卟啉单胞菌可诱导KB细胞MMP去极化和凋亡。此外，牙龈卟啉单胞菌在凋亡过程中上调AIF，但不激活caspase-3。此外，AIF抑制剂N-苯基马来酰亚胺几乎抑制牙龈卟啉单胞菌诱导的细胞凋亡。结论：牙龈卟啉单胞菌通过降解整合素β 1破坏上皮细胞粘附，并诱导不依赖半胱天冬酶的AIF介导的线粒体凋亡，这可能促进口腔组织的损伤。
Background: Porphyromonas gingivalis, a major pathogen of chronic periodontitis, adheres to and invades epithelial cells via an interaction between fimbriae and integrin. P. gingivalis proliferation and infection may affect the survival of cells. In this study, we further examined alternative signaling pathways mediating epithelial-cell death induced by P. gingivalis and the role of the cell-adhesion molecule integrin. Methods: Human epithelial KB cells interacted with P. gingivalis to evaluate cell death by Annexin V-propidium iodide (PI) staining. JC-1 staining was used to measure mitochondrial membrane potential (MMP). The mRNA and protein of integrin beta 1, apoptosis-inducing factor (AIF) and caspase-3 were detected by real-time PCR and western blot. Caspase-3 activity was analyzed by spectrophotometry. Results: P. gingivalis infection downregulated integrin beta 1 and led to cell detachment in a dose and time-dependent manner. Large amount of P. gingivalis induced MMP depolarization and apoptosis in KB cells. Moreover, P. gingivalis up-regulated AIF, but not activate caspase-3 during apoptosis. In addition, AIF inhibitor N-Phenylmaleimide almost inhibited the P. gingivalis-induced apoptosis. Conclusions: P. gingivalis disrupts epithelial-cell adhesion by degrading integrin beta 1 and induces caspase-independent, AIF-mediated mitochondrial apoptosis, which may promote the damage of oral tissue.