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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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 |
format | Article |
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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.</description><identifier>ISSN: 0014-4886</identifier><identifier>EISSN: 1090-2430</identifier><identifier>DOI: 10.1016/j.expneurol.2009.08.018</identifier><identifier>PMID: 19716366</identifier><identifier>CODEN: EXNEAC</identifier><language>eng</language><publisher>Amsterdam: Elsevier Inc</publisher><subject>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</subject><ispartof>Experimental neurology, 2009-11, Vol.220 (1), p.183-190</ispartof><rights>2009</rights><rights>2009 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c534t-f4b6c4c73ae35b238eb37252054e7d208b14209b3b34c60d8257830384c102b53</citedby><cites>FETCH-LOGICAL-c534t-f4b6c4c73ae35b238eb37252054e7d208b14209b3b34c60d8257830384c102b53</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0014488609003574$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,776,780,881,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=22058460$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19716366$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhou, Zhigang</creatorcontrib><creatorcontrib>Peng, Xiangmin</creatorcontrib><creatorcontrib>Insolera, Ryan</creatorcontrib><creatorcontrib>Fink, David J.</creatorcontrib><creatorcontrib>Mata, Marina</creatorcontrib><title>IL-10 promotes neuronal survival following spinal cord injury</title><title>Experimental neurology</title><addtitle>Exp Neurol</addtitle><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.</description><subject>Animals</subject><subject>Anti-Inflammatory Agents - metabolism</subject><subject>Apoptosis</subject><subject>Apoptosis Regulatory Proteins - metabolism</subject><subject>Biological and medical sciences</subject><subject>Cell Survival - genetics</subject><subject>Cells, Cultured</subject><subject>Cytokine</subject><subject>Disease Models, Animal</subject><subject>Female</subject><subject>Gene therapy</subject><subject>Genetic Therapy - methods</subject><subject>Genetic Vectors - pharmacology</subject><subject>Genetic Vectors - therapeutic use</subject><subject>Herpes simplex virus</subject><subject>Injuries of the nervous system and the skull. Diseases due to physical agents</subject><subject>Interleukin-10</subject><subject>Interleukin-10 - genetics</subject><subject>Interleukin-10 - metabolism</subject><subject>Medical sciences</subject><subject>Nerve Degeneration - etiology</subject><subject>Nerve Degeneration - physiopathology</subject><subject>Nerve Degeneration - prevention & control</subject><subject>Neurology</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Receptors, Interleukin-10 - genetics</subject><subject>Receptors, Interleukin-10 - metabolism</subject><subject>Signal Transduction - genetics</subject><subject>Signal Transduction - immunology</subject><subject>Simplexvirus - genetics</subject><subject>Spinal Cord - immunology</subject><subject>Spinal Cord - metabolism</subject><subject>Spinal Cord Injuries - genetics</subject><subject>Spinal Cord Injuries - immunology</subject><subject>Spinal Cord Injuries - therapy</subject><subject>Spinal cord injury</subject><subject>Transfection - methods</subject><subject>Traumas. Diseases due to physical agents</subject><subject>Treatment Outcome</subject><issn>0014-4886</issn><issn>1090-2430</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU1v1DAQhi1ERZfCX4Bc4JZ0_BHbOYBUVXxUWqkXOFuO4xSvvHawky3993i7q4WeehpL8_idd-ZF6D2GBgPml5vG_pmCXVL0DQHoGpANYPkCrTB0UBNG4SVaAWBWMyn5OXqd8wYKyIh4hc5xJzCnnK_Qp5t1jaGaUtzG2ebqUTNoX-Ul7dyuPMbofbx34a7Kk9t3TExD5cJmSQ9v0NmofbZvj_UC_fz65cf193p9--3m-mpdm5ayuR5Zzw0zgmpL255QaXsqSEugZVYMBGSPGYGupz1lhsMgSSskBSqZwUD6ll6gzwfdaem3djA2zEl7NSW31elBRe3U005wv9Rd3CkipOywLAIfjwIp_l5sntXWZWO918HGJSsueBmI4VmQYFK8SlJAcQBNijknO57cYFD7jNRGnTJS-4wUSAWPXt79v8y_f8dQCvDhCOhstB-TDsblE0fK3STje69XB86W0--cTSobZ4Oxg0vWzGqI7lkzfwF2Z7QZ</recordid><startdate>20091101</startdate><enddate>20091101</enddate><creator>Zhou, Zhigang</creator><creator>Peng, Xiangmin</creator><creator>Insolera, Ryan</creator><creator>Fink, David J.</creator><creator>Mata, Marina</creator><general>Elsevier Inc</general><general>Elsevier</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TK</scope><scope>7U9</scope><scope>H94</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20091101</creationdate><title>IL-10 promotes neuronal survival following spinal cord injury</title><author>Zhou, Zhigang ; Peng, Xiangmin ; Insolera, Ryan ; Fink, David J. ; Mata, Marina</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c534t-f4b6c4c73ae35b238eb37252054e7d208b14209b3b34c60d8257830384c102b53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Animals</topic><topic>Anti-Inflammatory Agents - metabolism</topic><topic>Apoptosis</topic><topic>Apoptosis Regulatory Proteins - metabolism</topic><topic>Biological and medical sciences</topic><topic>Cell Survival - genetics</topic><topic>Cells, Cultured</topic><topic>Cytokine</topic><topic>Disease Models, Animal</topic><topic>Female</topic><topic>Gene therapy</topic><topic>Genetic Therapy - methods</topic><topic>Genetic Vectors - pharmacology</topic><topic>Genetic Vectors - therapeutic use</topic><topic>Herpes simplex virus</topic><topic>Injuries of the nervous system and the skull. Diseases due to physical agents</topic><topic>Interleukin-10</topic><topic>Interleukin-10 - genetics</topic><topic>Interleukin-10 - metabolism</topic><topic>Medical sciences</topic><topic>Nerve Degeneration - etiology</topic><topic>Nerve Degeneration - physiopathology</topic><topic>Nerve Degeneration - prevention & control</topic><topic>Neurology</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Receptors, Interleukin-10 - genetics</topic><topic>Receptors, Interleukin-10 - metabolism</topic><topic>Signal Transduction - genetics</topic><topic>Signal Transduction - immunology</topic><topic>Simplexvirus - genetics</topic><topic>Spinal Cord - immunology</topic><topic>Spinal Cord - metabolism</topic><topic>Spinal Cord Injuries - genetics</topic><topic>Spinal Cord Injuries - immunology</topic><topic>Spinal Cord Injuries - therapy</topic><topic>Spinal cord injury</topic><topic>Transfection - methods</topic><topic>Traumas. 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. 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.</abstract><cop>Amsterdam</cop><pub>Elsevier Inc</pub><pmid>19716366</pmid><doi>10.1016/j.expneurol.2009.08.018</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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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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