Gliovascular and cytokine interactions modulate brain endothelial barrier in vitro

Ganta V. Chaitanya, Walter E. Cromer, Shannon R. Wells, Merilyn H. Jennings, P. Olivier Couraud, Ignacio A. Romero, Babette Weksler, Anat Erdreich-Epstein, James Michael Mathis, Alireza Minagar, J. Steven Alexander

Research output: Contribution to journalArticleResearchpeer-review

25 Citations (Scopus)

Abstract

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 in vitro 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).

Original languageEnglish
Article number162
JournalJournal of Neuroinflammation
Volume8
DOIs
StatePublished - 23 Nov 2011

Fingerprint

Cytokines
Brain
Astrocytes
Blood-Brain Barrier
Coculture Techniques
Endothelial Cells
Focal Adhesions
In Vitro Techniques
Matrix Metalloproteinases
Electric Impedance
Interleukin-1
Oxidants
Endothelium
Blood Vessels
Cell Survival
Homeostasis

Keywords

  • Astrocytes
  • Brain endothelium
  • Co-culture
  • Ifn-γ
  • Il-1β
  • Mono-culture
  • Tnf-α

Cite this

Chaitanya, G. V., Cromer, W. E., Wells, S. R., Jennings, M. H., Couraud, P. O., Romero, I. A., ... Alexander, J. S. (2011). Gliovascular and cytokine interactions modulate brain endothelial barrier in vitro. Journal of Neuroinflammation, 8, [162]. https://doi.org/10.1186/1742-2094-8-162
Chaitanya, Ganta V. ; Cromer, Walter E. ; Wells, Shannon R. ; Jennings, Merilyn H. ; Couraud, P. Olivier ; Romero, Ignacio A. ; Weksler, Babette ; Erdreich-Epstein, Anat ; Mathis, James Michael ; Minagar, Alireza ; Alexander, J. Steven. / Gliovascular and cytokine interactions modulate brain endothelial barrier in vitro. In: Journal of Neuroinflammation. 2011 ; Vol. 8.
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abstract = "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 in vitro 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).",
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Chaitanya, GV, Cromer, WE, Wells, SR, Jennings, MH, Couraud, PO, Romero, IA, Weksler, B, Erdreich-Epstein, A, Mathis, JM, Minagar, A & Alexander, JS 2011, 'Gliovascular and cytokine interactions modulate brain endothelial barrier in vitro', Journal of Neuroinflammation, vol. 8, 162. https://doi.org/10.1186/1742-2094-8-162

Gliovascular and cytokine interactions modulate brain endothelial barrier in vitro. / Chaitanya, Ganta V.; Cromer, Walter E.; Wells, Shannon R.; Jennings, Merilyn H.; Couraud, P. Olivier; Romero, Ignacio A.; Weksler, Babette; Erdreich-Epstein, Anat; Mathis, James Michael; Minagar, Alireza; Alexander, J. Steven.

In: Journal of Neuroinflammation, Vol. 8, 162, 23.11.2011.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Gliovascular and cytokine interactions modulate brain endothelial barrier in vitro

AU - Chaitanya, Ganta V.

AU - Cromer, Walter E.

AU - Wells, Shannon R.

AU - Jennings, Merilyn H.

AU - Couraud, P. Olivier

AU - Romero, Ignacio A.

AU - Weksler, Babette

AU - Erdreich-Epstein, Anat

AU - Mathis, James Michael

AU - Minagar, Alireza

AU - Alexander, J. Steven

PY - 2011/11/23

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N2 - 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 in vitro 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).

AB - 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 in vitro 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).

KW - Astrocytes

KW - Brain endothelium

KW - Co-culture

KW - Ifn-γ

KW - Il-1β

KW - Mono-culture

KW - Tnf-α

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U2 - 10.1186/1742-2094-8-162

DO - 10.1186/1742-2094-8-162

M3 - Article

VL - 8

JO - Journal of Neuroinflammation

JF - Journal of Neuroinflammation

SN - 1742-2094

M1 - 162

ER -

Chaitanya GV, Cromer WE, Wells SR, Jennings MH, Couraud PO, Romero IA et al. Gliovascular and cytokine interactions modulate brain endothelial barrier in vitro. Journal of Neuroinflammation. 2011 Nov 23;8. 162. https://doi.org/10.1186/1742-2094-8-162