title: 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.affiliation: Unitat de Neuroimmunologia Clínica, Department of Neurology, Hospital General Vall d'Hebron, Barcelona, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Espejo
authors.forename: J
authors.initials: J
authors.lastname: Carrasco
authors.forename: J
authors.initials: J
authors.lastname: Hidalgo
authors.forename: M
authors.initials: M
authors.lastname: Penkowa
authors.forename: A
authors.initials: A
authors.lastname: Garcia
authors.forename: I
authors.initials: I
authors.lastname: Sáez-Torres
authors.forename: E M
authors.initials: EM
authors.lastname: Martínez-Cáceres
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D002490:Central Nervous System / Q000378:metabolism*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000378:metabolism* / Q000473:pathology; D005260:Female; D008264:Macrophages / Q000378:metabolism; D008297:Male; D008668:Metallothionein / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics; D017628:Microglia / Q000378:metabolism; D020033:Protein Isoforms / Q000378:metabolism; D017471:Receptors, Interferon / Q000172:deficiency / Q000235:genetics; D000096743:Interferon gamma Receptor
chemical_list: D008668:Metallothionein; D020033:Protein Isoforms; D017471:Receptors, Interferon; D000096743:Interferon gamma Receptor