Title:The Effect of Dexamethasone on Lipopolysaccharide-induced Inflammation
of Endothelial Cells of the Blood-brain Barrier/Brain Capillaries
Volume: 20
Issue: 3
Author(s): Tershlin Jeftha, Khayelihle Brian Makhathini and David Fisher*
Affiliation:
- Neurobiology Research Group, Department of Medical Biosciences, Faculty of Natural Sciences, University of the
Western Cape, Bellville, Cape Town, 7535, South Africa
Keywords:
Blood-brain barrier, inflammation, tight junctions, permeability, integrity, central nervous system.
Abstract:
Background: A protective and regulatory barrier between the blood and the brain is
constituted by the blood-brain barrier (BBB), which comprises microvascular endothelial cells
providing homeostatic regulation of the central nervous system (CNS). Inflammation compromises
the BBB and contributes to many CNS disorders. Anti-inflammatory effects are exerted by glucocorticoids
(GCs) on a variety of cells. These GCs include dexamethasone (Dex), which is used for
the treatment of inflammatory diseases and recently for the treatment of COVID-19.
Aim: The purpose of this study was to determine whether low or high concentrations of Dex can attenuate
the inflammatory response induced by lipopolysaccharide (LPS) in the in vitro BBB model.
Methods: Brain endothelial cells (bEnd.5) were cultured and exposed to LPS (100ng/ml) and subsequently
co-treated with Dex to investigate whether selected concentrations of Dex (0.1, 5, 10,
20μM) can modulate the inflammatory effects of LPS on bEnd.5 cells. Cell viability, cell toxicity,
and cell proliferation were investigated, as well as the monitoring of membrane permeability (Trans
Endothelial Electrical Resistance-TEER), and Enzyme-Linked Immune Assay (ELISA) kits were
used to identify and quantify the presence of inflammatory cytokines (TNF-α and IL-1β).
Results: Dex, at a lower dosage (0.1μM, but not higher doses), was able to attenuate the inflammatory
effects of LPS on bEnd.5 cells. Lower doses of Dex (0.1μM) had no detrimental effects on
bEnd.5 cells, while higher Dex doses (5-20μM) decreased bEnd.5 viability, increased bEnd.5 cell
toxicity, increased bEnd.5 cell monolayer permeability, and increased proinflammatory cytokine
secretion.
Conclusion: These results indicate that treatment of brain vascular inflammation with low doses of
Dex should be advocated, while higher doses promote vascular inflammation.
