IL-10 promotes neuronal survival following spinal cord injury

We have previously reported that the anti-inflammatory cytokine IL-10 induces a number of signaling cascades through the IL-10 receptor in spinal cord neurons in vitro to activate NF-κB transcription Bcl-2 and Bcl-x L and that, after exposure to glutamate IL-10, blocks cytochrome c release and caspa...

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Veröffentlicht in:Experimental neurology 2009-11, Vol.220 (1), p.183-190
Hauptverfasser: Zhou, Zhigang, Peng, Xiangmin, Insolera, Ryan, Fink, David J., Mata, Marina
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container_issue 1
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container_title Experimental neurology
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creator Zhou, Zhigang
Peng, Xiangmin
Insolera, Ryan
Fink, David J.
Mata, Marina
description We have previously reported that the anti-inflammatory cytokine IL-10 induces a number of signaling cascades through the IL-10 receptor in spinal cord neurons in vitro to activate NF-κB transcription Bcl-2 and Bcl-x L and that, after exposure to glutamate IL-10, blocks cytochrome c release and caspase cleavage. In the current study we used a herpes simplex virus (HSV)-based vector to express IL-10 in spinal cord in vivo. Injection of the vector 30 minutes after lateral hemisection injury resulted in increased neuronal survival in the anterior quadrant of the spinal cord and improved motor function up to 6 weeks after injury, that correlated with translocation of p50 and p65 NF-κB to the nucleus and increased expression of Bcl-2 and Bcl-x L in anterior quadrant neurons. Inhibition of cytochrome c release and caspase 3 cleavage was seen in homogenates of injured spinal cord treated by the IL-10 vector. Taken together with in vitro studies that demonstrate direct neuroprotective effects of IL-10 acting through the neuronal IL-10 receptor, these results suggest that IL-10 may provide direct neuroprotective effects in spinal cord injury separate from and in addition to the known anti-inflammatory effects and point to the possibility that IL-10 delivery by gene transfer may be a useful adjunctive therapy for spinal cord injury.
doi_str_mv 10.1016/j.expneurol.2009.08.018
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In the current study we used a herpes simplex virus (HSV)-based vector to express IL-10 in spinal cord in vivo. Injection of the vector 30 minutes after lateral hemisection injury resulted in increased neuronal survival in the anterior quadrant of the spinal cord and improved motor function up to 6 weeks after injury, that correlated with translocation of p50 and p65 NF-κB to the nucleus and increased expression of Bcl-2 and Bcl-x L in anterior quadrant neurons. Inhibition of cytochrome c release and caspase 3 cleavage was seen in homogenates of injured spinal cord treated by the IL-10 vector. 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Diseases due to physical agents</topic><topic>Treatment Outcome</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhou, Zhigang</creatorcontrib><creatorcontrib>Peng, Xiangmin</creatorcontrib><creatorcontrib>Insolera, Ryan</creatorcontrib><creatorcontrib>Fink, David J.</creatorcontrib><creatorcontrib>Mata, Marina</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Experimental neurology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhou, Zhigang</au><au>Peng, Xiangmin</au><au>Insolera, Ryan</au><au>Fink, David J.</au><au>Mata, Marina</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>IL-10 promotes neuronal survival following spinal cord injury</atitle><jtitle>Experimental neurology</jtitle><addtitle>Exp Neurol</addtitle><date>2009-11-01</date><risdate>2009</risdate><volume>220</volume><issue>1</issue><spage>183</spage><epage>190</epage><pages>183-190</pages><issn>0014-4886</issn><eissn>1090-2430</eissn><coden>EXNEAC</coden><abstract>We have previously reported that the anti-inflammatory cytokine IL-10 induces a number of signaling cascades through the IL-10 receptor in spinal cord neurons in vitro to activate NF-κB transcription Bcl-2 and Bcl-x L and that, after exposure to glutamate IL-10, blocks cytochrome c release and caspase cleavage. 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subjects Animals
Anti-Inflammatory Agents - metabolism
Apoptosis
Apoptosis Regulatory Proteins - metabolism
Biological and medical sciences
Cell Survival - genetics
Cells, Cultured
Cytokine
Disease Models, Animal
Female
Gene therapy
Genetic Therapy - methods
Genetic Vectors - pharmacology
Genetic Vectors - therapeutic use
Herpes simplex virus
Injuries of the nervous system and the skull. Diseases due to physical agents
Interleukin-10
Interleukin-10 - genetics
Interleukin-10 - metabolism
Medical sciences
Nerve Degeneration - etiology
Nerve Degeneration - physiopathology
Nerve Degeneration - prevention & control
Neurology
Rats
Rats, Sprague-Dawley
Receptors, Interleukin-10 - genetics
Receptors, Interleukin-10 - metabolism
Signal Transduction - genetics
Signal Transduction - immunology
Simplexvirus - genetics
Spinal Cord - immunology
Spinal Cord - metabolism
Spinal Cord Injuries - genetics
Spinal Cord Injuries - immunology
Spinal Cord Injuries - therapy
Spinal cord injury
Transfection - methods
Traumas. Diseases due to physical agents
Treatment Outcome
title IL-10 promotes neuronal survival following spinal cord injury
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