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Activated Microglia Disrupt the Blood-Brain Barrier and Induce Chemokines and Cytokines in a Rat in vitro Model

Severe neuroinflammation is associated with blood brain barrier (BBB) disruption in CNS diseases. Although microglial activation and the subsequent changes in cytokine/chemokine (C/C) concentrations are thought to be key steps in the development of neuroinflammation, little data are available concer...

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Autores principales: Shigemoto-Mogami, Yukari, Hoshikawa, Kazue, Sato, Kaoru
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6300509/
https://www.ncbi.nlm.nih.gov/pubmed/30618641
http://dx.doi.org/10.3389/fncel.2018.00494
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author Shigemoto-Mogami, Yukari
Hoshikawa, Kazue
Sato, Kaoru
author_facet Shigemoto-Mogami, Yukari
Hoshikawa, Kazue
Sato, Kaoru
author_sort Shigemoto-Mogami, Yukari
collection PubMed
description Severe neuroinflammation is associated with blood brain barrier (BBB) disruption in CNS diseases. Although microglial activation and the subsequent changes in cytokine/chemokine (C/C) concentrations are thought to be key steps in the development of neuroinflammation, little data are available concerning the interaction of microglia with BBB cells. In this study, we investigated this interaction by adding LPS-activated microglia (LPS-MG) to the abluminal side of a BBB model composed of endothelial cells (EC), pericytes (Peri) and astrocytes (Ast). We then examined the abluminal concentrations of 27 C/Cs and the interactions between the LPS-MG and BBB cells. LPS-MG caused collapse of the BBB, revealed by decreases in the trans-endothelial electrical resistance (TEER) and by changes in the expression levels of tight junction (TJ) proteins. Under these conditions, 19 C/Cs were markedly increased on the abluminal side. Unexpectedly, although LPS-MG alone released 10 of the 19 C/Cs, their concentrations were much lower than those detected on the abluminal side of the BBB model supplemented with LPS-MG. Co-culture of LPS-MG with Ast caused marked increases in 12 of the 19 C/Cs, while co-culture of LPS-MG with EC and Peri resulted in a significant increase in only 1 of the 19 C/Cs (fractalkine). These results suggest that C/C dynamics in this system are not only caused by activated microglia but also are due to the interaction between activated microglia and astrocytes.
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spelling pubmed-63005092019-01-07 Activated Microglia Disrupt the Blood-Brain Barrier and Induce Chemokines and Cytokines in a Rat in vitro Model Shigemoto-Mogami, Yukari Hoshikawa, Kazue Sato, Kaoru Front Cell Neurosci Neuroscience Severe neuroinflammation is associated with blood brain barrier (BBB) disruption in CNS diseases. Although microglial activation and the subsequent changes in cytokine/chemokine (C/C) concentrations are thought to be key steps in the development of neuroinflammation, little data are available concerning the interaction of microglia with BBB cells. In this study, we investigated this interaction by adding LPS-activated microglia (LPS-MG) to the abluminal side of a BBB model composed of endothelial cells (EC), pericytes (Peri) and astrocytes (Ast). We then examined the abluminal concentrations of 27 C/Cs and the interactions between the LPS-MG and BBB cells. LPS-MG caused collapse of the BBB, revealed by decreases in the trans-endothelial electrical resistance (TEER) and by changes in the expression levels of tight junction (TJ) proteins. Under these conditions, 19 C/Cs were markedly increased on the abluminal side. Unexpectedly, although LPS-MG alone released 10 of the 19 C/Cs, their concentrations were much lower than those detected on the abluminal side of the BBB model supplemented with LPS-MG. Co-culture of LPS-MG with Ast caused marked increases in 12 of the 19 C/Cs, while co-culture of LPS-MG with EC and Peri resulted in a significant increase in only 1 of the 19 C/Cs (fractalkine). These results suggest that C/C dynamics in this system are not only caused by activated microglia but also are due to the interaction between activated microglia and astrocytes. Frontiers Media S.A. 2018-12-13 /pmc/articles/PMC6300509/ /pubmed/30618641 http://dx.doi.org/10.3389/fncel.2018.00494 Text en Copyright © 2018 Shigemoto-Mogami, Hoshikawa and Sato. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Shigemoto-Mogami, Yukari
Hoshikawa, Kazue
Sato, Kaoru
Activated Microglia Disrupt the Blood-Brain Barrier and Induce Chemokines and Cytokines in a Rat in vitro Model
title Activated Microglia Disrupt the Blood-Brain Barrier and Induce Chemokines and Cytokines in a Rat in vitro Model
title_full Activated Microglia Disrupt the Blood-Brain Barrier and Induce Chemokines and Cytokines in a Rat in vitro Model
title_fullStr Activated Microglia Disrupt the Blood-Brain Barrier and Induce Chemokines and Cytokines in a Rat in vitro Model
title_full_unstemmed Activated Microglia Disrupt the Blood-Brain Barrier and Induce Chemokines and Cytokines in a Rat in vitro Model
title_short Activated Microglia Disrupt the Blood-Brain Barrier and Induce Chemokines and Cytokines in a Rat in vitro Model
title_sort activated microglia disrupt the blood-brain barrier and induce chemokines and cytokines in a rat in vitro model
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6300509/
https://www.ncbi.nlm.nih.gov/pubmed/30618641
http://dx.doi.org/10.3389/fncel.2018.00494
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