<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:	Vichuda Charoensaensuk, Yen-Chou Chen, Yun-Ho Lin, Keng-Liang Ou, Liang-Yo Yang, Dah-Yuu Lu
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	<i>P. gingivalis</i> ROS NAC cell apoptosis proinflammatory cytokine Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/7b8483fc8d7841dd9cf18d42df0e3c8f
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spelling	oai:doaj.org-article:7b8483fc8d7841dd9cf18d42df0e3c8f2021-11-25T17:10:44Z<i>Porphyromonas gingivalis</i> Induces Proinflammatory Cytokine Expression Leading to Apoptotic Death through the Oxidative Stress/NF-κB Pathway in Brain Endothelial Cells10.3390/cells101130332073-4409https://doaj.org/article/7b8483fc8d7841dd9cf18d42df0e3c8f2021-11-01T00:00:00Zhttps://www.mdpi.com/2073-4409/10/11/3033https://doaj.org/toc/2073-4409<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.Vichuda CharoensaensukYen-Chou ChenYun-Ho LinKeng-Liang OuLiang-Yo YangDah-Yuu LuMDPI AGarticle<i>P. gingivalis</i>ROSNACcell apoptosisproinflammatory cytokineBiology (General)QH301-705.5ENCells, Vol 10, Iss 3033, p 3033 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	<i>P. gingivalis</i> ROS NAC cell apoptosis proinflammatory cytokine Biology (General) QH301-705.5
spellingShingle	<i>P. gingivalis</i> ROS NAC cell apoptosis proinflammatory cytokine Biology (General) QH301-705.5 Vichuda Charoensaensuk Yen-Chou Chen Yun-Ho Lin Keng-Liang Ou Liang-Yo Yang Dah-Yuu Lu <i>Porphyromonas gingivalis</i> Induces Proinflammatory Cytokine Expression Leading to Apoptotic Death through the Oxidative Stress/NF-κB Pathway in Brain Endothelial Cells
description	<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.
format	article
author	Vichuda Charoensaensuk Yen-Chou Chen Yun-Ho Lin Keng-Liang Ou Liang-Yo Yang Dah-Yuu Lu
author_facet	Vichuda Charoensaensuk Yen-Chou Chen Yun-Ho Lin Keng-Liang Ou Liang-Yo Yang Dah-Yuu Lu
author_sort	Vichuda Charoensaensuk
title	<i>Porphyromonas gingivalis</i> Induces Proinflammatory Cytokine Expression Leading to Apoptotic Death through the Oxidative Stress/NF-κB Pathway in Brain Endothelial Cells
title_short	<i>Porphyromonas gingivalis</i> Induces Proinflammatory Cytokine Expression Leading to Apoptotic Death through the Oxidative Stress/NF-κB Pathway in Brain Endothelial Cells
title_full	<i>Porphyromonas gingivalis</i> Induces Proinflammatory Cytokine Expression Leading to Apoptotic Death through the Oxidative Stress/NF-κB Pathway in Brain Endothelial Cells
title_fullStr	<i>Porphyromonas gingivalis</i> Induces Proinflammatory Cytokine Expression Leading to Apoptotic Death through the Oxidative Stress/NF-κB Pathway in Brain Endothelial Cells
title_full_unstemmed	<i>Porphyromonas gingivalis</i> Induces Proinflammatory Cytokine Expression Leading to Apoptotic Death through the Oxidative Stress/NF-κB Pathway in Brain Endothelial Cells
title_sort	<i>porphyromonas gingivalis</i> induces proinflammatory cytokine expression leading to apoptotic death through the oxidative stress/nf-κb pathway in brain endothelial cells
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/7b8483fc8d7841dd9cf18d42df0e3c8f
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<i>Porphyromonas gingivalis</i> Induces Proinflammatory Cytokine Expression Leading to Apoptotic Death through the Oxidative Stress/NF-κB Pathway in Brain Endothelial Cells

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