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IL-6 Induced by Periodontal Inflammation Causes Neuroinflammation and Disrupts the Blood–Brain Barrier

Background: Periodontal disease (PD) is a risk factor for systemic diseases, including neurodegenerative diseases. The role of the local and systemic inflammation induced by PD in neuroinflammation currently remains unclear. The present study investigated the involvement of periodontal inflammation...

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Autores principales: Furutama, Daisuke, Matsuda, Shinji, Yamawaki, Yosuke, Hatano, Saki, Okanobu, Ai, Memida, Takumi, Oue, Hiroshi, Fujita, Tsuyoshi, Ouhara, Kazuhisa, Kajiya, Mikihito, Mizuno, Noriyoshi, Kanematsu, Takashi, Tsuga, Kazuhiro, Kurihara, Hidemi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7599694/
https://www.ncbi.nlm.nih.gov/pubmed/32992470
http://dx.doi.org/10.3390/brainsci10100679
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author Furutama, Daisuke
Matsuda, Shinji
Yamawaki, Yosuke
Hatano, Saki
Okanobu, Ai
Memida, Takumi
Oue, Hiroshi
Fujita, Tsuyoshi
Ouhara, Kazuhisa
Kajiya, Mikihito
Mizuno, Noriyoshi
Kanematsu, Takashi
Tsuga, Kazuhiro
Kurihara, Hidemi
author_facet Furutama, Daisuke
Matsuda, Shinji
Yamawaki, Yosuke
Hatano, Saki
Okanobu, Ai
Memida, Takumi
Oue, Hiroshi
Fujita, Tsuyoshi
Ouhara, Kazuhisa
Kajiya, Mikihito
Mizuno, Noriyoshi
Kanematsu, Takashi
Tsuga, Kazuhiro
Kurihara, Hidemi
author_sort Furutama, Daisuke
collection PubMed
description Background: Periodontal disease (PD) is a risk factor for systemic diseases, including neurodegenerative diseases. The role of the local and systemic inflammation induced by PD in neuroinflammation currently remains unclear. The present study investigated the involvement of periodontal inflammation in neuroinflammation and blood–brain barrier (BBB) disruption. Methods: To induce PD in mice (c57/BL6), a ligature was placed around the second maxillary molar. Periodontal, systemic, and neuroinflammation were assessed based on the inflammatory cytokine mRNA or protein levels using qPCR and ELISA. The BBB permeability was evaluated by the mRNA levels and protein levels of tight junction-related proteins in the hippocampus using qPCR and immunofluorescence. Dextran tracing in the hippocampus was also conducted to examine the role of periodontal inflammation in BBB disruption. Results: The TNF-α, IL-1β, and IL-6 levels markedly increased in gingival tissue 1 week after ligation. The IL-6 serum levels were also increased by ligature-induced PD. In the hippocampus, the IL-1β mRNA expression levels were significantly increased by ligature-induced PD through serum IL-6. The ligature-induced PD decreased the claudin 5 expression levels in the hippocampus, and the neutralization of IL-6 restored its levels. The extravascular 3-kDa dextran levels were increased by ligature-induced PD. Conclusions: These results suggest that the periodontal inflammation-induced expression of IL-6 is related to neuroinflammation and BBB disruption in the hippocampus, ultimately leading to cognitive impairment. Periodontal therapy may protect against neurodegenerative diseases.
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spelling pubmed-75996942020-11-01 IL-6 Induced by Periodontal Inflammation Causes Neuroinflammation and Disrupts the Blood–Brain Barrier Furutama, Daisuke Matsuda, Shinji Yamawaki, Yosuke Hatano, Saki Okanobu, Ai Memida, Takumi Oue, Hiroshi Fujita, Tsuyoshi Ouhara, Kazuhisa Kajiya, Mikihito Mizuno, Noriyoshi Kanematsu, Takashi Tsuga, Kazuhiro Kurihara, Hidemi Brain Sci Article Background: Periodontal disease (PD) is a risk factor for systemic diseases, including neurodegenerative diseases. The role of the local and systemic inflammation induced by PD in neuroinflammation currently remains unclear. The present study investigated the involvement of periodontal inflammation in neuroinflammation and blood–brain barrier (BBB) disruption. Methods: To induce PD in mice (c57/BL6), a ligature was placed around the second maxillary molar. Periodontal, systemic, and neuroinflammation were assessed based on the inflammatory cytokine mRNA or protein levels using qPCR and ELISA. The BBB permeability was evaluated by the mRNA levels and protein levels of tight junction-related proteins in the hippocampus using qPCR and immunofluorescence. Dextran tracing in the hippocampus was also conducted to examine the role of periodontal inflammation in BBB disruption. Results: The TNF-α, IL-1β, and IL-6 levels markedly increased in gingival tissue 1 week after ligation. The IL-6 serum levels were also increased by ligature-induced PD. In the hippocampus, the IL-1β mRNA expression levels were significantly increased by ligature-induced PD through serum IL-6. The ligature-induced PD decreased the claudin 5 expression levels in the hippocampus, and the neutralization of IL-6 restored its levels. The extravascular 3-kDa dextran levels were increased by ligature-induced PD. Conclusions: These results suggest that the periodontal inflammation-induced expression of IL-6 is related to neuroinflammation and BBB disruption in the hippocampus, ultimately leading to cognitive impairment. Periodontal therapy may protect against neurodegenerative diseases. MDPI 2020-09-27 /pmc/articles/PMC7599694/ /pubmed/32992470 http://dx.doi.org/10.3390/brainsci10100679 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Furutama, Daisuke
Matsuda, Shinji
Yamawaki, Yosuke
Hatano, Saki
Okanobu, Ai
Memida, Takumi
Oue, Hiroshi
Fujita, Tsuyoshi
Ouhara, Kazuhisa
Kajiya, Mikihito
Mizuno, Noriyoshi
Kanematsu, Takashi
Tsuga, Kazuhiro
Kurihara, Hidemi
IL-6 Induced by Periodontal Inflammation Causes Neuroinflammation and Disrupts the Blood–Brain Barrier
title IL-6 Induced by Periodontal Inflammation Causes Neuroinflammation and Disrupts the Blood–Brain Barrier
title_full IL-6 Induced by Periodontal Inflammation Causes Neuroinflammation and Disrupts the Blood–Brain Barrier
title_fullStr IL-6 Induced by Periodontal Inflammation Causes Neuroinflammation and Disrupts the Blood–Brain Barrier
title_full_unstemmed IL-6 Induced by Periodontal Inflammation Causes Neuroinflammation and Disrupts the Blood–Brain Barrier
title_short IL-6 Induced by Periodontal Inflammation Causes Neuroinflammation and Disrupts the Blood–Brain Barrier
title_sort il-6 induced by periodontal inflammation causes neuroinflammation and disrupts the blood–brain barrier
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7599694/
https://www.ncbi.nlm.nih.gov/pubmed/32992470
http://dx.doi.org/10.3390/brainsci10100679
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