Metallothionein-I overexpression decreases brain pathology in transgenic mice with astrocyte-targeted expression of interleukin-6

Amalia Molinero, Milena Penkowa, Joaquín Hernández, Jordi Camats, Mercedes Giralt, Natalia Lago, Javier Carrasco, Iain L. Campbell, Juan Hidalgo

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34 Citations (Scopus)

Abstract

Transgenic expression of interleukin-6 (IL-6) in the CNS under the control of the glial fibrillary acidic protein (GFAP) gene promoter (GFAP-IL6 mice) causes significant damage and alters the expression of many genes, including a dramatic upregulation of metallothionein-I (MT-I). The findings in this report support the idea that the upregulation of MT-I observed in GFAP-IL6 mice is an important mechanism for coping with brain damage. Thus, GFAP-IL6 mice that were crossed with TgMTI transgenic mice (GFAP-IL6xTgMTI) and overexpressed MT-I in the brain showed a decreased upregulation of cytokines such as IL-6 and a diminished recruitment and activation of macrophages and T cells throughout the CNS but mainly in the cerebellum. The GFAP-IL6 mice showed clear evidence of increased oxidative stress, which was significantly decreased by MT-I overexpression. Interestingly. MT-I overexpression increased angiogenesis in GFAP-IL6 mice but not in control littermates. Overall, the results strongly suggest that MT-I+II proteins are valuable factors that protect against cytokine-induced CNS injury.
Original languageEnglish
Pages (from-to)315-328
JournalJournal of Neuropathology and Experimental Neurology
Volume62
Issue number3
DOIs
Publication statusPublished - 1 Mar 2003

Keywords

  • Angiogenesis
  • Cytokines
  • IL-6
  • Metallothionein
  • Oxidative stress

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    Molinero, A., Penkowa, M., Hernández, J., Camats, J., Giralt, M., Lago, N., Carrasco, J., Campbell, I. L., & Hidalgo, J. (2003). Metallothionein-I overexpression decreases brain pathology in transgenic mice with astrocyte-targeted expression of interleukin-6. Journal of Neuropathology and Experimental Neurology, 62(3), 315-328. https://doi.org/10.1093/jnen/62.3.315