Chaitanya, Ganta V.; Cromer, Walter E.; Wells, Shannon R.; Jennings, Merilyn H.; Couraud, P. Oliver; Romero, Ignacio A; Weksler, Babette; Erdreich-Epstein, Anat; Mathis, James Michael; Minagar, Alireza and Alexander, J. Steven
(2011).
Gliovascular and cytokine interactions modulate brain endothelial barrier in vitro.
Journal of Neuroinflammation, 8(162),
(
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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-alpha, IL-1 beta or IFN-gamma 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).
| Item Type: |
Journal Article
|
| Copyright Holders: |
2011 Chaitanya et al. ; licensee BioMed Central Ltd. |
| ISSN: |
1742-2094 |
| Funders: |
Post‐doctoral fellowship support from the 'Feist Cardiovascular Research Endowment, LSUHSC‐Shreveport, NIH DK43785 grant |
| Keywords: |
TNF‐α; IL‐1β; IFN‐γ; brain endothelium; astrocytes; co‐culture; mono‐Culture |
| Academic Unit/Department: |
Science > Life, Health and Chemical Sciences |
| Related URLs: |
|
| Item ID: |
30558 |
| Depositing User: |
Ignacio A Romero
|
| Date Deposited: |
13 Dec 2011 16:31 |
| Last Modified: |
14 Nov 2012 11:56 |
| URI: |
http://oro.open.ac.uk/id/eprint/30558 |
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