Astrocyte-targeted expression of interleukin-6 protects the central nervous system during neuroglial degeneration induced by 6-aminonicotinamide

Milena Penkowa, Jordi Camats, Hanne Hadberg, Albert Quintana, Santiago Rojas, Mercedes Giralt, Amalia Molinero, Iain L. Campbell, Juan Hidalgo

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54 Citations (Scopus)

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-α as well as growth factors basic fibroblast growth factor (bFGF), transforming growth factor-β, 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. © 2003 Wiley-Liss, Inc.
Original languageEnglish
Pages (from-to)481-496
JournalJournal of Neuroscience Research
Volume73
DOIs
Publication statusPublished - 15 Aug 2003

Keywords

  • Apoptosis
  • Neuropathology
  • Neuroprotection
  • Oxidative stress

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