Metallothionein-I overexpression alters brain inflammation and stimulates brain repair in transgenic mice with astrocyte - Targeted interleukin-6 expression

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

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

39 Citations (Scopus)

Abstract

Transgenic expression of IL-6 in the CNS under the control of the GFAP gene promoter, glial fibrillary acidic protein-interleukin-6 (GFAP-IL-6) mice, raises an inflammatory response and causes significant brain damage. However, the results obtained in the GFAP-IL-6 mice after a traumatic brain injury, such as a cryolesion, demonstrate a neuroprotective role of IL-6. Thus, the GFAP-IL-6 mice showed faster tissue repair and decreased oxidative stress and apoptosis compared with control litter-mate mice. The neuroprotective factors metallothionein-I+II (MT-I+II) were upregulated by the cryolesion to a higher extent in the GFAP-IL-6 mice, suggesting that they could be related to the neuroprotection afforded by the transgenic expression of IL-6. To examine this possibility, we have crossed GFAP-IL-6 mice with transgenic mice overexpressing MT-I (TgMT), producing double transgenic GFAP-IL-6 TgMT mice. The results obtained after cryolesion in GFAP-IL-6 TgMT mice, as well as in TgMT mice, consistently supported the idea that the increased MT-I+II levels observed in GFAP-IL-6 mice are a fundamental and important mechanism for coping with brain damage. Accordingly, MT-I overexpression regulated the inflammatory response, decreased oxidative stress and apoptosis significantly, and increased brain tissue repair in comparison with either GFAP-IL-6 or control litter-mate mice. Overall, the results demonstrate that brain MT-I+II proteins are fundamental neuroprotective factors. © 2003 Wiley-Liss, Inc.
Original languageEnglish
Pages (from-to)287-306
JournalGLIA
Volume42
DOIs
Publication statusPublished - 1 May 2003

Keywords

  • Interleukin-6
  • Metallothionein-I
  • Overexpression
  • Transgenic mice

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