<i>Porphyromonas gingivalis</i> Induces Proinflammatory Cytokine Expression Leading to Apoptotic Death through the Oxidative Stress/NF-κB Pathway in Brain Endothelial Cells
<i>Porphyromonas gingivalis</i>, a periodontal pathogen, has been proposed to cause blood vessel injury leading to cerebrovascular diseases such as stroke. Brain endothelial cells compose the blood-brain barrier that protects homeostasis of the central nervous system. However, whether &l...
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| Autores principales: | , , , , , |
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| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
MDPI AG
2021
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| Materias: | |
| Acceso en línea: | https://doaj.org/article/7b8483fc8d7841dd9cf18d42df0e3c8f |
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| Sumario: | <i>Porphyromonas gingivalis</i>, a periodontal pathogen, has been proposed to cause blood vessel injury leading to cerebrovascular diseases such as stroke. Brain endothelial cells compose the blood-brain barrier that protects homeostasis of the central nervous system. However, whether <i>P. gingivalis</i> causes the death of endothelial cells and the underlying mechanisms remain unclear. This study aimed to investigate the impact and regulatory mechanisms of <i>P. gingivalis</i> infection in brain endothelial cells. We used bEnd.3 cells and primary mouse endothelial cells to assess the effects of <i>P. gingivalis</i> on endothelial cells. Our results showed that infection with live <i>P. gingivalis</i>, unlike heat-killed <i>P. gingivalis</i>, triggers brain endothelial cell death by inducing cell apoptosis. Moreover, <i>P. gingivalis</i> infection increased intracellular reactive oxygen species (ROS) production, activated NF-κB, and up-regulated the expression of IL-1β and TNF-α. Furthermore, <i>N</i>-acetyl-L-cysteine (NAC), a most frequently used antioxidant, treatment significantly reduced <i>P. gingivalis-</i>induced cell apoptosis and brain endothelial cell death. The enhancement of ROS production, NF-κB p65 activation, and proinflammatory cytokine expression was also attenuated by NAC treatment. The impact of <i>P. gingivalis</i> on brain endothelial cells was also confirmed using adult primary mouse brain endothelial cells (MBECs). In summary, our results showed that <i>P. gingivalis</i> up-regulates IL-1β and TNF-α protein expression, which consequently causes cell death of brain endothelial cells through the ROS/NF-κB pathway. Our results, together with the results of previous case-control studies and epidemiologic reports, strongly support the hypothesis that periodontal infection increases the risk of developing cerebrovascular disease. |
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