Metallothionein-I overexpression decreases brain pathology in transgenic mice with astrocyte-targeted expression of interleukin-6
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Metallothionein-I overexpression decreases brain pathology in transgenic mice with astrocyte-targeted expression of interleukin-6. / Molinero, Amalia; Penkowa, Milena; Hernández, Joaquín; Camats, Jordi; Giralt, Mercedes; Lago, Natalia; Carrasco, Javier; Campbell, Iain L; Hidalgo, Juan.
In: Journal of Neuropathology and Experimental Neurology, Vol. 62, No. 3, 2003, p. 315-28.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Metallothionein-I overexpression decreases brain pathology in transgenic mice with astrocyte-targeted expression of interleukin-6
AU - Molinero, Amalia
AU - Penkowa, Milena
AU - Hernández, Joaquín
AU - Camats, Jordi
AU - Giralt, Mercedes
AU - Lago, Natalia
AU - Carrasco, Javier
AU - Campbell, Iain L
AU - Hidalgo, Juan
N1 - Keywords: Animals; Astrocytes; Brain; Female; Gene Expression Regulation; Glial Fibrillary Acidic Protein; Interleukin-6; Male; Metallothionein; Mice; Mice, Inbred C57BL; Mice, Transgenic; Up-Regulation
PY - 2003
Y1 - 2003
N2 - 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.
AB - 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.
M3 - Journal article
C2 - 12638735
VL - 62
SP - 315
EP - 328
JO - Journal of Neuropathology and Experimental Neurology
JF - Journal of Neuropathology and Experimental Neurology
SN - 0022-3069
IS - 3
ER -
ID: 13620646