Myelin basic protein induces inflammatory mediators from primary human endothelial cells and blood–brain barrier disruption: implications for the pathogenesis of multiple sclerosis

Abstract

Aim Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS), characterized by demyelination of white matter, loss of myelin forming oligodendrocytes, changes in the blood-brain-barrier (BBB), and leukocyte infiltration. Myelin basic protein (MBP) is a component of the myelin sheath. Degradation of myelin is believed to be an important step that leads to MS pathology. Transmigration of leukocytes across the vasculature, and a compromised BBB participate in the neuroinflammation of MS. We examined the expression and regulation of the chemokine CCL2 and the cytokine IL-6 in human endothelial cells (EC), a component of the BBB, after treatment with MBP. Methods EC were treated with full length MBP. CCL2 and IL-6 protein were determined by ELISA. Western blot analysis was used to determine signaling pathways. A BBB model was treated with MBP and permeability was assayed using albumin conjugated to Evan’s blue dye. The levels of the tight junction proteins occludin and claudin-1, and matrix metalloprotease (MMP)-2 were assayed by Western blot. Results MBP significantly induced CCL2 and IL-6 protein from EC. This induction was partially mediated by the p38 MAPK pathway as there was phosphorylation after MBP treatment. MBP treatment of a BBB model caused an increase in permeability that correlated with a decrease in occludin and claudin-1, and an induction of MMP-2. Conclusion These data demonstrate that MBP induces chemotactic and inflammatory mediators. MBP also alters BBB permeability and tight junction expression, indicating additional factors that may contribute to the BBB breakdown characteristic of MS.

Protective Effect of Electroacupuncture on Neural Myelin Sheaths is Mediated via Promotion of Oligodendrocyte Proliferation and Inhibition of Oligodendrocyte Death After Compressed Spinal Cord Injury

“…The BBB scores of rats in EA for 14 days group were remarkably increased when compared with EA for 7 days group and control for 14 days group. To investigate whether or not EA can protect oligodendrocyte cells from death, we examined MBP which is synthesized by oligodendrocyte on free polysomes in the cytoplasm [24,25] at the lesion site in different groups by Western blot. No statistically significant differences were found in the baseline studies between the control and EA groups (p>0.05).…”

iPSC-derived neural precursors exert a neuroprotective role in immune-mediated demyelination via the secretion of LIF

“…As a direct consequence of this phenomenon axonal regeneration and remyelination are inhibited 24 and BBB permeability altered 25 . Transcriptomics and functional annotation data-indicating that transcripts involved in cell survival/death processes were differentially regulated in miPSC-NPC transplanted EAE mice at 40 dpi (Fig.…”

The Use of Agmatine Provides the New Insight in an Experimental Model of Multiple Sclerosis

“…AGM-after 20 dpi), ***p [ 0.05, (EAEw vs EAEk-after 24 dpi), One Way ANOVA, Dunnett's C test elevated production of MMP-3 and MMP-9. Compromised BBB facilitates the influx of inflammatory cells which enhance neuroinflammation [41]. Agmatine application post EAE induces MMP-3 and MMP-9 depletion in both WT and KO animals (Figs.…”