Myelin basic protein induces inflammatory mediators from primary human endothelial cells and blood-brain barrier disruption

Implications for the pathogenesis of multiple sclerosis

T. G. D'Aversa, Eliseo Eugenin, L. Lopez, J. W. Berman

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

T. G. D'Aversa, E. A. Eugenin, L. Lopez and J. W. Berman (2013) Neuropathology and Applied Neurobiology39, 270-283 Myelin basic protein induces inflammatory mediators from primary human endothelial cells and blood-brain barrier disruption: implications for the pathogenesis of multiple sclerosis Aim: Multiple sclerosis (MS) is an autoimmune disease of the central nervous system, characterized by demyelination of white matter, loss of myelin forming oligodendrocytes, changes in the blood-brain barrier (BBB) and leucocyte 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 leucocytes across the vasculature, and a compromised BBB participate in the neuroinflammation of MS. We examined the expression and regulation of the chemokine (C-C motif) ligand 2 (CCL2) and the cytokine interleukin-6 (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 signalling 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 MMP2. 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.

Original languageEnglish (US)
Pages (from-to)270-283
Number of pages14
JournalNeuropathology and Applied Neurobiology
Volume39
Issue number3
DOIs
StatePublished - Apr 1 2013
Externally publishedYes

Fingerprint

Myelin Basic Protein
Blood-Brain Barrier
Multiple Sclerosis
Endothelial Cells
Myelin Sheath
Claudin-1
Occludin
Permeability
Interleukin-6
Leukocytes
Autoimmune Diseases of the Nervous System
Western Blotting
Ligands
Tight Junction Proteins
Evans Blue
Chemokine CCL2
Tight Junctions
Oligodendroglia
Metalloproteases
Demyelinating Diseases

Keywords

  • Blood-brain barrier
  • CCL2
  • EAE
  • IL-6
  • MBP
  • MS

ASJC Scopus subject areas

  • Clinical Neurology
  • Pathology and Forensic Medicine
  • Neurology
  • Histology
  • Physiology (medical)

Cite this

@article{aba7662cb38644d2974cf3de336d08db,
title = "Myelin basic protein induces inflammatory mediators from primary human endothelial cells and blood-brain barrier disruption: Implications for the pathogenesis of multiple sclerosis",
abstract = "T. G. D'Aversa, E. A. Eugenin, L. Lopez and J. W. Berman (2013) Neuropathology and Applied Neurobiology39, 270-283 Myelin basic protein induces inflammatory mediators from primary human endothelial cells and blood-brain barrier disruption: implications for the pathogenesis of multiple sclerosis Aim: Multiple sclerosis (MS) is an autoimmune disease of the central nervous system, characterized by demyelination of white matter, loss of myelin forming oligodendrocytes, changes in the blood-brain barrier (BBB) and leucocyte 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 leucocytes across the vasculature, and a compromised BBB participate in the neuroinflammation of MS. We examined the expression and regulation of the chemokine (C-C motif) ligand 2 (CCL2) and the cytokine interleukin-6 (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 signalling 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 MMP2. 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.",
keywords = "Blood-brain barrier, CCL2, EAE, IL-6, MBP, MS",
author = "D'Aversa, {T. G.} and Eliseo Eugenin and L. Lopez and Berman, {J. W.}",
year = "2013",
month = "4",
day = "1",
doi = "10.1111/j.1365-2990.2012.01279.x",
language = "English (US)",
volume = "39",
pages = "270--283",
journal = "Neuropathology and Applied Neurobiology",
issn = "0305-1846",
publisher = "Wiley-Blackwell",
number = "3",

}

TY - JOUR

T1 - Myelin basic protein induces inflammatory mediators from primary human endothelial cells and blood-brain barrier disruption

T2 - Implications for the pathogenesis of multiple sclerosis

AU - D'Aversa, T. G.

AU - Eugenin, Eliseo

AU - Lopez, L.

AU - Berman, J. W.

PY - 2013/4/1

Y1 - 2013/4/1

N2 - T. G. D'Aversa, E. A. Eugenin, L. Lopez and J. W. Berman (2013) Neuropathology and Applied Neurobiology39, 270-283 Myelin basic protein induces inflammatory mediators from primary human endothelial cells and blood-brain barrier disruption: implications for the pathogenesis of multiple sclerosis Aim: Multiple sclerosis (MS) is an autoimmune disease of the central nervous system, characterized by demyelination of white matter, loss of myelin forming oligodendrocytes, changes in the blood-brain barrier (BBB) and leucocyte 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 leucocytes across the vasculature, and a compromised BBB participate in the neuroinflammation of MS. We examined the expression and regulation of the chemokine (C-C motif) ligand 2 (CCL2) and the cytokine interleukin-6 (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 signalling 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 MMP2. 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.

AB - T. G. D'Aversa, E. A. Eugenin, L. Lopez and J. W. Berman (2013) Neuropathology and Applied Neurobiology39, 270-283 Myelin basic protein induces inflammatory mediators from primary human endothelial cells and blood-brain barrier disruption: implications for the pathogenesis of multiple sclerosis Aim: Multiple sclerosis (MS) is an autoimmune disease of the central nervous system, characterized by demyelination of white matter, loss of myelin forming oligodendrocytes, changes in the blood-brain barrier (BBB) and leucocyte 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 leucocytes across the vasculature, and a compromised BBB participate in the neuroinflammation of MS. We examined the expression and regulation of the chemokine (C-C motif) ligand 2 (CCL2) and the cytokine interleukin-6 (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 signalling 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 MMP2. 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.

KW - Blood-brain barrier

KW - CCL2

KW - EAE

KW - IL-6

KW - MBP

KW - MS

UR - http://www.scopus.com/inward/record.url?scp=84866176888&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84866176888&partnerID=8YFLogxK

U2 - 10.1111/j.1365-2990.2012.01279.x

DO - 10.1111/j.1365-2990.2012.01279.x

M3 - Article

VL - 39

SP - 270

EP - 283

JO - Neuropathology and Applied Neurobiology

JF - Neuropathology and Applied Neurobiology

SN - 0305-1846

IS - 3

ER -