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

doi:10.1002/jnr.10681

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

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

57 Citationer (Scopus)

Abstract

Udgivelsesdato: 2003-Aug-15

Originalsprog	Engelsk
Tidsskrift	Journal of Neuroscience Research
Vol/bind	73
Udgave nummer	4
Sider (fra-til)	481-96
Antal sider	15
ISSN	0360-4012
DOI	https://doi.org/10.1002/jnr.10681
Status	Udgivet - 2003

Bibliografisk note

Adgang til dokumentet

10.1002/jnr.10681

Citationsformater

Astrocyte-targeted expression of interleukin-6 protects the central nervous system during neuroglial degeneration induced by 6-aminonicotinamide. / Penkowa, Milena; Camats, Jordi; Hadberg, Hanne; Quintana, Albert; Rojas, Santiago; Giralt, Mercedes; Molinero, Amalia; Campbell, Iain L; Hidalgo, Juan.

I: Journal of Neuroscience Research, Bind 73, Nr. 4, 2003, s. 481-96.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

Penkowa, Milena ; Camats, Jordi ; Hadberg, Hanne ; Quintana, Albert ; Rojas, Santiago ; Giralt, Mercedes ; Molinero, Amalia ; Campbell, Iain L ; Hidalgo, Juan. / Astrocyte-targeted expression of interleukin-6 protects the central nervous system during neuroglial degeneration induced by 6-aminonicotinamide. I: Journal of Neuroscience Research. 2003 ; Bind 73, Nr. 4. s. 481-96.

@article{4fab6ac0832b11de8bc9000ea68e967b,

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

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.",

author = "Milena Penkowa and Jordi Camats and Hanne Hadberg and Albert Quintana and Santiago Rojas and Mercedes Giralt and Amalia Molinero and Campbell, {Iain L} and Juan Hidalgo",

note = "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",

year = "2003",

doi = "10.1002/jnr.10681",

language = "English",

volume = "73",

pages = "481--96",

journal = "Journal of Neuroscience Research",

issn = "0360-4012",

publisher = "JohnWiley & Sons, Inc.",

number = "4",

}

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

VL - 73

SP - 481

EP - 496

JO - Journal of Neuroscience Research

JF - Journal of Neuroscience Research

SN - 0360-4012

IS - 4

ER -