Caspase-11 mediates oligodendrocyte cell death and pathogenesis of autoimmune-mediated demyelination

S. Hisahara, J. Yuan, T. Momoi, Hideyuki Okano, M. Miura

Research output: Contribution to journalArticle

95 Citations (Scopus)

Abstract

Multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE), are inflammatory diseases of the central nervous system (CNS) characterized by localized areas of demyelination. The mechanisms underlying oligodendrocyte (OLG) injury in MS and EAE remain unknown. Here we show that caspase-11 plays crucial roles in OLG death and pathogenesis in EAE. Caspase-11 and activated caspase-3 were both expressed in OLGs in spinal cord EAE lesions. OLGs from caspase-11-deficient mice were highly resistant to the cell death induced by cytotoxic cytokines. EAE susceptibility and cytokine concentrations in the CNS were significantly reduced in caspase-11-deficient mice. Our findings suggest that OLG death is mediated by a pathway that involves caspases-11 and -3 and leads to the demyelination observed in EAE.

Original languageEnglish
Pages (from-to)111-122
Number of pages12
JournalJournal of Experimental Medicine
Volume193
Issue number1
DOIs
Publication statusPublished - 2001 Jan 1
Externally publishedYes

Fingerprint

Autoimmune Experimental Encephalomyelitis
Oligodendroglia
Demyelinating Diseases
Caspases
Cell Death
Caspase 3
Multiple Sclerosis
Cytokines
Central Nervous System Diseases
Spinal Cord
Central Nervous System
Animal Models
Wounds and Injuries

Keywords

  • Apoptosis
  • Cytokines
  • Experimental autoimmune encephalomyelitis
  • Knockout mouse
  • Multiple sclerosis

ASJC Scopus subject areas

  • Immunology

Cite this

Caspase-11 mediates oligodendrocyte cell death and pathogenesis of autoimmune-mediated demyelination. / Hisahara, S.; Yuan, J.; Momoi, T.; Okano, Hideyuki; Miura, M.

In: Journal of Experimental Medicine, Vol. 193, No. 1, 01.01.2001, p. 111-122.

Research output: Contribution to journalArticle

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