Gliovascular and cytokine interactions modulate brain endothelial barrier <it>in vitro</it>

<p>Abstract</p> <p>The glio-vascular unit (G-unit) plays a prominent role in maintaining homeostasis of the blood-brain barrier (BBB) and disturbances in cells forming this unit may seriously dysregulate BBB. The direct and indirect effects of cytokines on cellular components of th...

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Main Authors: Chaitanya Ganta V, Cromer Walter E, Wells Shannon R, Jennings Merilyn H, Couraud P Olivier, Romero Ignacio A, Weksler Babette, Erdreich-Epstein Anat, Mathis J Michael, Minagar Alireza, Alexander J Steven
Format: Article
Language:English
Published: BMC 2011-11-01
Series:Journal of Neuroinflammation
Subjects:
Online Access:http://www.jneuroinflammation.com/content/8/1/162
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author Chaitanya Ganta V
Cromer Walter E
Wells Shannon R
Jennings Merilyn H
Couraud P Olivier
Romero Ignacio A
Weksler Babette
Erdreich-Epstein Anat
Mathis J Michael
Minagar Alireza
Alexander J Steven
author_facet Chaitanya Ganta V
Cromer Walter E
Wells Shannon R
Jennings Merilyn H
Couraud P Olivier
Romero Ignacio A
Weksler Babette
Erdreich-Epstein Anat
Mathis J Michael
Minagar Alireza
Alexander J Steven
author_sort Chaitanya Ganta V
collection DOAJ
description <p>Abstract</p> <p>The glio-vascular unit (G-unit) plays a prominent role in maintaining homeostasis of the blood-brain barrier (BBB) and disturbances in cells forming this unit may seriously dysregulate BBB. The direct and indirect effects of cytokines on cellular components of the BBB are not yet unclear. The present study compares the effects of cytokines and cytokine-treated astrocytes on brain endothelial barrier. 3-dimensional transwell co-cultures of brain endothelium and related-barrier forming cells with astrocytes were used to investigate gliovascular barrier responses to cytokines during pathological stresses. Gliovascular barrier was measured using trans-endothelial electrical resistance (TEER), a sensitive index of <it>in vitro </it>barrier integrity. We found that neither TNF-α, IL-1β or IFN-γ directly reduced barrier in human or mouse brain endothelial cells or ECV-304 barrier (independent of cell viability/metabolism), but found that astrocyte exposure to cytokines in co-culture significantly reduced endothelial (and ECV-304) barrier. These results indicate that the barrier established by human and mouse brain endothelial cells (and other cells) may respond positively to cytokines alone, but that during pathological conditions, cytokines dysregulate the barrier forming cells indirectly through astrocyte activation involving reorganization of junctions, matrix, focal adhesion or release of barrier modulating factors (e.g. oxidants, MMPs).</p>
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spelling doaj.art-cadb4363a0b5479cb61508bd5a9c88142022-12-21T19:13:08ZengBMCJournal of Neuroinflammation1742-20942011-11-018116210.1186/1742-2094-8-162Gliovascular and cytokine interactions modulate brain endothelial barrier <it>in vitro</it>Chaitanya Ganta VCromer Walter EWells Shannon RJennings Merilyn HCouraud P OlivierRomero Ignacio AWeksler BabetteErdreich-Epstein AnatMathis J MichaelMinagar AlirezaAlexander J Steven<p>Abstract</p> <p>The glio-vascular unit (G-unit) plays a prominent role in maintaining homeostasis of the blood-brain barrier (BBB) and disturbances in cells forming this unit may seriously dysregulate BBB. The direct and indirect effects of cytokines on cellular components of the BBB are not yet unclear. The present study compares the effects of cytokines and cytokine-treated astrocytes on brain endothelial barrier. 3-dimensional transwell co-cultures of brain endothelium and related-barrier forming cells with astrocytes were used to investigate gliovascular barrier responses to cytokines during pathological stresses. Gliovascular barrier was measured using trans-endothelial electrical resistance (TEER), a sensitive index of <it>in vitro </it>barrier integrity. We found that neither TNF-α, IL-1β or IFN-γ directly reduced barrier in human or mouse brain endothelial cells or ECV-304 barrier (independent of cell viability/metabolism), but found that astrocyte exposure to cytokines in co-culture significantly reduced endothelial (and ECV-304) barrier. These results indicate that the barrier established by human and mouse brain endothelial cells (and other cells) may respond positively to cytokines alone, but that during pathological conditions, cytokines dysregulate the barrier forming cells indirectly through astrocyte activation involving reorganization of junctions, matrix, focal adhesion or release of barrier modulating factors (e.g. oxidants, MMPs).</p>http://www.jneuroinflammation.com/content/8/1/162TNF-αIL-1βIFN-γBrain endotheliumAstrocytesCo-cultureMono-Culture
spellingShingle Chaitanya Ganta V
Cromer Walter E
Wells Shannon R
Jennings Merilyn H
Couraud P Olivier
Romero Ignacio A
Weksler Babette
Erdreich-Epstein Anat
Mathis J Michael
Minagar Alireza
Alexander J Steven
Gliovascular and cytokine interactions modulate brain endothelial barrier <it>in vitro</it>
Journal of Neuroinflammation
TNF-α
IL-1β
IFN-γ
Brain endothelium
Astrocytes
Co-culture
Mono-Culture
title Gliovascular and cytokine interactions modulate brain endothelial barrier <it>in vitro</it>
title_full Gliovascular and cytokine interactions modulate brain endothelial barrier <it>in vitro</it>
title_fullStr Gliovascular and cytokine interactions modulate brain endothelial barrier <it>in vitro</it>
title_full_unstemmed Gliovascular and cytokine interactions modulate brain endothelial barrier <it>in vitro</it>
title_short Gliovascular and cytokine interactions modulate brain endothelial barrier <it>in vitro</it>
title_sort gliovascular and cytokine interactions modulate brain endothelial barrier it in vitro it
topic TNF-α
IL-1β
IFN-γ
Brain endothelium
Astrocytes
Co-culture
Mono-Culture
url http://www.jneuroinflammation.com/content/8/1/162
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