Gliovascular and cytokine interactions modulate brain endothelial barrier in vitro
- PDF / 913,500 Bytes
- 16 Pages / 595.28 x 793.7 pts Page_size
- 15 Downloads / 194 Views
JOURNAL OF NEUROINFLAMMATION
RESEARCH
Open Access
Gliovascular and cytokine interactions modulate brain endothelial barrier in vitro Ganta V Chaitanya1, Walter E Cromer2, Shannon R Wells1, Merilyn H Jennings1, P Olivier Couraud4,5,6, Ignacio A Romero7, Babette Weksler7, Anat Erdreich-Epstein9, J Michael Mathis2, Alireza Minagar3 and J Steven Alexander1,8*
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-a, IL-1b or IFN-g 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). Keywords: TNF-α, IL-1β, IFN-γ, Brain endothelium, Astrocytes, Co-culture, Mono-Culture
Background The blood brain barrier (BBB) is a unique astrocytecapillary-endothelial complex which maintains CNS homeostatic fluid balance, and serves as a first line of defense protecting the brain and parenchyma against pathogens, as well as blood-borne leukocytes and hormones, neurotransmitters and pro-inflammatory cytokines and chemokines [1,2]. The loss of BBB structural integrity and function plays a central role in the pathogenesis of neuroinflammatory diseases like multiple sclerosis, Alzheimer’s disease, meningitis, brain tumors, intracerebral hemorrhage and stroke [3-10]. Many reports in the literature indicate that loss of BBB in neuroinflammation represents a result of complex often continuous interactions between the BBB and immune * Correspondence: [email protected] 1 Department of Molecular and Cellular Physiology, School of Graduate Studies, Louisiana State University Health Sciences Center-Shreveport, 1501 Kings Hwy, Shreveport, LA 71130, USA Full list of author information is available at the end of the article
cells, adhesive determinants and inflammatory cytokines, all of which may be relevant targets for therapy [11-18].
Data Loading...
