Differential expression of metallothioneins in the CNS of mice with experimental autoimmune encephalomyelitis.

Abstract

Multiple sclerosis is an inflammatory, demyelinating disease of the CNS. Metallothioneins-I+II are antioxidant proteins induced in the CNS by immobilisation stress, trauma or degenerative diseases which have been postulated to play a neuroprotective role, while the CNS isoform metallothionein-III has been related to Alzheimer's disease. We have analysed metallothioneins-I-III expression in the CNS of mice with experimental autoimmune encephalomyelitis. Moreover, we have examined the putative role of interferon-gamma, a pro-inflammatory cytokine, in the control of metallothioneins expression during experimental autoimmune encephalomyelitis in interferon-gamma receptor knockout mice with two different genetic backgrounds: 129/Sv and C57BL/6x129/Sv. Mice with experimental autoimmune encephalomyelitis showed a significant induction of metallothioneins-I+II in the spinal cord white matter, and to a lower extent in the brain. Interferon-gamma receptor knockout mice suffered from a more severe experimental autoimmune encephalomyelitis, and interestingly showed a higher metallothioneins-I+II induction in both white and grey matter of the spinal cord and in the brain. In contrast to the metallothioneins-I+II isoforms, metallothionein-III expression remained essentially unaltered during experimental autoimmune encephalomyelitis; interferon-gamma receptor knockout mice showed an altered metallothionein-III expression (a slight increase in the spinal cord white matter) only in the C57BL/6x129/Sv background. Metallothioneins-I+II proteins were prominent in areas of induced cellular infiltrates. Reactive astrocytes and activated monocytes/macrophages were the sources of metallothioneins-I+II proteins. From these results we suggest that metallothioneins-I+II but not metallothionein-III may play an important role during experimental autoimmune encephalomyelitis, and indicate that the pro-inflammatory cytokine interferon-gamma is unlikely an important factor in this response.

• Authors: C Espejo, J Carrasco, J Hidalgo, M Penkowa, A Garcia, I Sáez-Torres, E M Martínez-Cáceres
• Journal: Neuroscience (Neuroscience) Vol. 105 Issue 4 Pg. 1055-65 ( 2001) ISSN: 0306-4522 [Print] United States
• PMID: 11530242 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Protein Isoforms
• Receptors, Interferon
• interferon gamma receptor
• Metallothionein

Topics

• Animals
• Astrocytes (metabolism)
• Central Nervous System (metabolism)
• Encephalomyelitis, Autoimmune, Experimental (metabolism, pathology)
• Female
• Macrophages (metabolism)
• Male
• Metallothionein (metabolism)
• Mice
• Mice, Knockout (genetics)
• Microglia (metabolism)
• Protein Isoforms (metabolism)
• Receptors, Interferon (deficiency, genetics)