Gliovascular and cytokine interactions modulate brain endothelial barrier in vitro

Journal of Neuroinflammation

J Steven Alexander⁵  Alireza Minagar¹  J Michael Mathis⁷  Anat Erdreich-Epstein²  Babette Weksler³  Ignacio A Romero³  P Olivier Couraud⁴  Merilyn H Jennings⁶  Shannon R Wells⁶  Walter E Cromer⁷  Ganta V Chaitanya⁶ 

[1] Department of Neurology, School of Medicine, Louisiana State University Health Sciences Center-Shreveport, 1501 Kings Hwy, Shreveport, LA 71130, USA;Division of Hematology-Oncology, Departments of Pediatrics and Pathology, The Saban Research Institute at Children's Hospital Los Angeles and Keck School of Medicine, University of Southern California, 4650 Sunset Boulevard, Los Angeles, California 90027, USA;Department of Biological Sciences, The Open University, Milton Keynes, UK;Univ Paris Descartes, Paris, France;Department of Medicine, Weill Medical College, 1300 York Ave, New York, NY-10065, USA;Department of Molecular and Cellular Physiology, School of Graduate Studies, Louisiana State University Health Sciences Center-Shreveport, 1501 Kings Hwy, Shreveport, LA 71130, USA;Cell Biology and Anatomy, School of Graduate Studies, Louisiana State University Health Sciences Center-Shreveport, 1501 Kings Hwy, Shreveport, LA 71130, USA

关键词: Mono-Culture;    Co-culture;    Astrocytes;    Brain endothelium;    IFN-γ;    IL-1β;    TNF-α;   

Others  :  1212996
DOI  :  10.1186/1742-2094-8-162

 received in 2011-05-10, accepted in 2011-11-23,  发布年份 2011

【 摘 要 】

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).

【 授权许可】

   
2011 Chaitanya et al; licensee BioMed Central Ltd.

【 图 表 】

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