Increased severity of experimental autoimmune encephalomyelitis, chronic macrophage/microglial reactivity, and demyelination in transgenic mice producing tumor necrosis factor-α in the central nervous system

Véronique Taupin, Toufic Renno, Lyne Bourbonnière, Alan C. Peterson, Moses Rodriguez, Trevor Owens

Research output: Contribution to journalArticle

128 Citations (Scopus)

Abstract

Tumor necrosis factor-α (TNF-α) is an inflammatory cytokine implicated in a number of autoimmune diseases. Apoptotic cell death is induced by TNF-α in vitro, and has been suggested as one cause of autoimmune pathology, including autoimmune demyelinating diseases where oligodendrocytes are a target of immune attack. TNF-α also regulates macrophage activity which could contribute to autoimmune inflammation. We have expressed TNF-α at disease-equivalent levels in the central nervous system of transgenic mice, using a myelin basic protein (MBP) promoter. These mice were normal and showed no spontaneous pathology, but they developed experimental autoimmune encephalomyelitis (EAE) with greater severity than nontransgenic controls when immunized with MBP in adjuvant. Unlike nontransgenic controls, EAE then progressed to a nonabating demyelinating disease. Macrophage/microglial reactivity was evident in demyelinating lesions in spinal cord, but T cells were not detected during chronic disease. The participation of TNF-α in the demyelinating process is thus more probably due to the perpetuation of macrophage/microglial activation than to direct cytotoxicity of myelin or oligodendroglia.

Original languageEnglish (US)
Pages (from-to)905-913
Number of pages9
JournalEuropean Journal of Immunology
Volume27
Issue number4
DOIs
StatePublished - 1997

Fingerprint

Autoimmune Experimental Encephalomyelitis
Demyelinating Diseases
Transgenic Mice
Central Nervous System
Tumor Necrosis Factor-alpha
Macrophages
Myelin Basic Protein
Oligodendroglia
Autoimmune Diseases
Pathology
Macrophage Activation
Myelin Sheath
Spinal Cord
Chronic Disease
Cell Death
Cytokines
Inflammation
T-Lymphocytes

Keywords

  • Demyelination
  • Macrophage
  • Microglia
  • Transgenic
  • Tumor necrosis factor-α

ASJC Scopus subject areas

  • Immunology

Cite this

Increased severity of experimental autoimmune encephalomyelitis, chronic macrophage/microglial reactivity, and demyelination in transgenic mice producing tumor necrosis factor-α in the central nervous system. / Taupin, Véronique; Renno, Toufic; Bourbonnière, Lyne; Peterson, Alan C.; Rodriguez, Moses; Owens, Trevor.

In: European Journal of Immunology, Vol. 27, No. 4, 1997, p. 905-913.

Research output: Contribution to journalArticle

@article{4769807130d94acd8658eb8a64b62ee5,
title = "Increased severity of experimental autoimmune encephalomyelitis, chronic macrophage/microglial reactivity, and demyelination in transgenic mice producing tumor necrosis factor-α in the central nervous system",
abstract = "Tumor necrosis factor-α (TNF-α) is an inflammatory cytokine implicated in a number of autoimmune diseases. Apoptotic cell death is induced by TNF-α in vitro, and has been suggested as one cause of autoimmune pathology, including autoimmune demyelinating diseases where oligodendrocytes are a target of immune attack. TNF-α also regulates macrophage activity which could contribute to autoimmune inflammation. We have expressed TNF-α at disease-equivalent levels in the central nervous system of transgenic mice, using a myelin basic protein (MBP) promoter. These mice were normal and showed no spontaneous pathology, but they developed experimental autoimmune encephalomyelitis (EAE) with greater severity than nontransgenic controls when immunized with MBP in adjuvant. Unlike nontransgenic controls, EAE then progressed to a nonabating demyelinating disease. Macrophage/microglial reactivity was evident in demyelinating lesions in spinal cord, but T cells were not detected during chronic disease. The participation of TNF-α in the demyelinating process is thus more probably due to the perpetuation of macrophage/microglial activation than to direct cytotoxicity of myelin or oligodendroglia.",
keywords = "Demyelination, Macrophage, Microglia, Transgenic, Tumor necrosis factor-α",
author = "V{\'e}ronique Taupin and Toufic Renno and Lyne Bourbonni{\`e}re and Peterson, {Alan C.} and Moses Rodriguez and Trevor Owens",
year = "1997",
doi = "10.1002/eji.1830270416",
language = "English (US)",
volume = "27",
pages = "905--913",
journal = "European Journal of Immunology",
issn = "0014-2980",
publisher = "Wiley-VCH Verlag",
number = "4",

}

TY - JOUR

T1 - Increased severity of experimental autoimmune encephalomyelitis, chronic macrophage/microglial reactivity, and demyelination in transgenic mice producing tumor necrosis factor-α in the central nervous system

AU - Taupin, Véronique

AU - Renno, Toufic

AU - Bourbonnière, Lyne

AU - Peterson, Alan C.

AU - Rodriguez, Moses

AU - Owens, Trevor

PY - 1997

Y1 - 1997

N2 - Tumor necrosis factor-α (TNF-α) is an inflammatory cytokine implicated in a number of autoimmune diseases. Apoptotic cell death is induced by TNF-α in vitro, and has been suggested as one cause of autoimmune pathology, including autoimmune demyelinating diseases where oligodendrocytes are a target of immune attack. TNF-α also regulates macrophage activity which could contribute to autoimmune inflammation. We have expressed TNF-α at disease-equivalent levels in the central nervous system of transgenic mice, using a myelin basic protein (MBP) promoter. These mice were normal and showed no spontaneous pathology, but they developed experimental autoimmune encephalomyelitis (EAE) with greater severity than nontransgenic controls when immunized with MBP in adjuvant. Unlike nontransgenic controls, EAE then progressed to a nonabating demyelinating disease. Macrophage/microglial reactivity was evident in demyelinating lesions in spinal cord, but T cells were not detected during chronic disease. The participation of TNF-α in the demyelinating process is thus more probably due to the perpetuation of macrophage/microglial activation than to direct cytotoxicity of myelin or oligodendroglia.

AB - Tumor necrosis factor-α (TNF-α) is an inflammatory cytokine implicated in a number of autoimmune diseases. Apoptotic cell death is induced by TNF-α in vitro, and has been suggested as one cause of autoimmune pathology, including autoimmune demyelinating diseases where oligodendrocytes are a target of immune attack. TNF-α also regulates macrophage activity which could contribute to autoimmune inflammation. We have expressed TNF-α at disease-equivalent levels in the central nervous system of transgenic mice, using a myelin basic protein (MBP) promoter. These mice were normal and showed no spontaneous pathology, but they developed experimental autoimmune encephalomyelitis (EAE) with greater severity than nontransgenic controls when immunized with MBP in adjuvant. Unlike nontransgenic controls, EAE then progressed to a nonabating demyelinating disease. Macrophage/microglial reactivity was evident in demyelinating lesions in spinal cord, but T cells were not detected during chronic disease. The participation of TNF-α in the demyelinating process is thus more probably due to the perpetuation of macrophage/microglial activation than to direct cytotoxicity of myelin or oligodendroglia.

KW - Demyelination

KW - Macrophage

KW - Microglia

KW - Transgenic

KW - Tumor necrosis factor-α

UR - http://www.scopus.com/inward/record.url?scp=0031003444&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031003444&partnerID=8YFLogxK

U2 - 10.1002/eji.1830270416

DO - 10.1002/eji.1830270416

M3 - Article

C2 - 9130643

AN - SCOPUS:0031003444

VL - 27

SP - 905

EP - 913

JO - European Journal of Immunology

JF - European Journal of Immunology

SN - 0014-2980

IS - 4

ER -