TY - JOUR
T1 - Astrocyte-targeted expression of interleukin-6 protects the central nervous system during neuroglial degeneration induced by 6-aminonicotinamide
AU - Penkowa, Milena
AU - Camats, Jordi
AU - Hadberg, Hanne
AU - Quintana, Albert
AU - Rojas, Santiago
AU - Giralt, Mercedes
AU - Molinero, Amalia
AU - Campbell, Iain L
AU - Hidalgo, Juan
N1 - Keywords: 6-Aminonicotinamide; Angiogenesis Inducing Agents; Animals; Apoptosis; Astrocytes; Brain Stem; Cell Count; Central Nervous System; Cytokines; Disease Models, Animal; Gene Targeting; Glial Fibrillary Acidic Protein; Growth Substances; Immunohistochemistry; In Situ Nick-End Labeling; Interleukin-6; Lymphocytes; Macrophages; Malondialdehyde; Metallothionein; Mice; Mice, Inbred C57BL; Mice, Transgenic; Microglia; Nerve Degeneration; Oxidative Stress; Staining and Labeling; Stem Cells; Teratogens; Tyrosine
PY - 2003
Y1 - 2003
N2 - 6-aminonicotinamide (6-AN) is a niacin antagonist, which leads to degeneration of gray matter astrocytes mainly in the brainstem. We have examined the role of interleukin-6 (IL-6) in this degenerative process by using transgenic mice with astrocyte-targeted IL-6 expression (GFAP-IL6 mice). This study demonstrates that transgenic IL-6 expression significantly increases the 6-AN-induced inflammatory response of reactive astrocytes, microglia/macrophages, and lymphocytes in the brainstem. Also, IL-6 induced significant increases in proinflammatory cytokines IL-1, IL-12, and tumor necrosis factor-alpha as well as growth factors basic fibroblast growth factor (bFGF), transforming growth factor-beta, neurotrophin-3, angiopoietin, vascular endothelial growth factor, and the receptor for bFGF. In accordance, angiogenesis was increased in GFAP-IL6 mice relative to controls after 6-AN. Moreover, oxidative stress and apoptotic cell death were significantly reduced by transgenic IL-6 expression. IL-6 is also a major inducer in the CNS of metallothionein I and II (MT-I+II), which were significantly increased in the GFAP-IL6 mice. MT-I+II are antioxidants and neuroregenerative factors in the CNS, so increased MT-I+II levels in GFAP-IL6 mice could contribute to the reduction of oxidative stress and cell death in these mice.
AB - 6-aminonicotinamide (6-AN) is a niacin antagonist, which leads to degeneration of gray matter astrocytes mainly in the brainstem. We have examined the role of interleukin-6 (IL-6) in this degenerative process by using transgenic mice with astrocyte-targeted IL-6 expression (GFAP-IL6 mice). This study demonstrates that transgenic IL-6 expression significantly increases the 6-AN-induced inflammatory response of reactive astrocytes, microglia/macrophages, and lymphocytes in the brainstem. Also, IL-6 induced significant increases in proinflammatory cytokines IL-1, IL-12, and tumor necrosis factor-alpha as well as growth factors basic fibroblast growth factor (bFGF), transforming growth factor-beta, neurotrophin-3, angiopoietin, vascular endothelial growth factor, and the receptor for bFGF. In accordance, angiogenesis was increased in GFAP-IL6 mice relative to controls after 6-AN. Moreover, oxidative stress and apoptotic cell death were significantly reduced by transgenic IL-6 expression. IL-6 is also a major inducer in the CNS of metallothionein I and II (MT-I+II), which were significantly increased in the GFAP-IL6 mice. MT-I+II are antioxidants and neuroregenerative factors in the CNS, so increased MT-I+II levels in GFAP-IL6 mice could contribute to the reduction of oxidative stress and cell death in these mice.
U2 - 10.1002/jnr.10681
DO - 10.1002/jnr.10681
M3 - Journal article
C2 - 12898533
SN - 0360-4012
VL - 73
SP - 481
EP - 496
JO - Journal of Neuroscience Research
JF - Journal of Neuroscience Research
IS - 4
ER -