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 language | English |
---|---|
Pages (from-to) | 315-328 |
Journal | Journal of Neuropathology and Experimental Neurology |
Volume | 62 |
Issue number | 3 |
DOIs | |
Publication status | Published - 1 Mar 2003 |
Keywords
- Angiogenesis
- Cytokines
- IL-6
- Metallothionein
- Oxidative stress