title: Gliovascular and cytokine interactions modulate brain endothelial barrier in vitro.
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).
authors: Department of Molecular and Cellular Physiology, School of Graduate Studies, Louisiana State University Health Sciences Center-Shreveport, 1501 Kings Hwy, Shreveport, LA 71130, USA.
authors: Ganta V
authors: GV
authors: Chaitanya
authors: Walter E
authors: WE
authors: Cromer
authors: Shannon R
authors: SR
authors: Wells
authors: Merilyn H
authors: MH
authors: Jennings
authors: P Olivier
authors: PO
authors: Couraud
authors: Ignacio A
authors: IA
authors: Romero
authors: Babette
authors: B
authors: Weksler
authors: Anat
authors: A
authors: Erdreich-Epstein
authors: J Michael
authors: JM
authors: Mathis
authors: Alireza
authors: A
authors: Minagar
authors: J Steven
authors: JS
authors: Alexander
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D001812:Blood-Brain Barrier / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D002199:Capillary Permeability / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000494:pharmacology*; D017097:Electric Impedance; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D053583:Interleukin-1beta / Q000494:pharmacology; D051379:Mice; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D016207:Cytokines; D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma