| First Author | Molinero A | Year | 2003 |
| Journal | J Neuropathol Exp Neurol | Volume | 62 |
| Issue | 3 | Pages | 315-28 |
| PubMed ID | 12638735 | Mgi Jnum | J:104847 |
| Mgi Id | MGI:3612912 | Doi | 10.1093/jnen/62.3.315 |
| Citation | Molinero A, et al. (2003) Metallothionein-I overexpression decreases brain pathology in transgenic mice with astrocyte-targeted expression of interleukin-6. J Neuropathol Exp Neurol 62(3):315-28 |
| abstractText | 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. |
