1. Astrocyte-targeted expression of interleukin-6 protects the central nervous system during neuroglial degeneration induced by 6-aminonicotinamide
- Author
-
Santiago Rojas, Amalia Molinero, Jordi Camats, Albert Quintana, Hanne Hadberg, Milena Penkowa, Juan Hidalgo, Iain L. Campbell, and Mercedes Giralt
- Subjects
Central Nervous System ,medicine.medical_specialty ,Programmed cell death ,Angiogenesis ,Basic fibroblast growth factor ,Apoptosis ,Cell Count ,Mice, Transgenic ,Biology ,Neuroprotection ,Proinflammatory cytokine ,Angiopoietin ,Mice ,Cellular and Molecular Neuroscience ,chemistry.chemical_compound ,Malondialdehyde ,Internal medicine ,Glial Fibrillary Acidic Protein ,In Situ Nick-End Labeling ,medicine ,Animals ,Lymphocytes ,Growth Substances ,Staining and Labeling ,Microglia ,Interleukin-6 ,Macrophages ,Stem Cells ,Immunohistochemistry ,Mice, Inbred C57BL ,Disease Models, Animal ,Oxidative Stress ,6-Aminonicotinamide ,Teratogens ,medicine.anatomical_structure ,Endocrinology ,chemistry ,Astrocytes ,Gene Targeting ,Nerve Degeneration ,Immunology ,Cytokines ,Tyrosine ,Angiogenesis Inducing Agents ,Metallothionein ,Tumor necrosis factor alpha ,Brain Stem - Abstract
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.
- Published
- 2003
- Full Text
- View/download PDF