Source:http://linkedlifedata.com/resource/pubmed/id/18322000
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
6
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pubmed:dateCreated |
2008-5-21
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pubmed:abstractText |
Glucocorticoid-induced tumor necrosis factor receptor-related (GITR) protein is a costimulatory molecule that plays a role in inflammation so that GITR-Fc fusion protein can exert an anti-inflammatory effect. To investigate the mechanism by which GITR-Fc exerts its effects, we first used GITR knock-out (GITR(-/-)) mice to verify whether GITR ligand (GITRL)/GITR system played a pro-inflammatory role in the spinal cord injury (SCI) model. It is noteworthy that less pronounced disease was induced in GITR(-/-) compared with GITR(+/+) mice. We then evaluated the effect of GITR-Fc fusion protein against SCI-induced injuries in GITR(-/-) and wild-type (GITR(+/+)) mice. Administration of GITR-Fc ameliorated SCI-induced inflammation in GITR(+/+) mice as evaluated through: 1) histological damage and apoptosis, 2) modulation of apoptosis-related transduction factors (Bax and Bcl-2), 3) expression of inflammatory markers [nitrotyrosine, inducible nitric-oxide synthase, interleukin (IL)-2, IL-12, and tumor necrosis factor-alpha], and 4) T-lymphocyte infiltration. GITR-Fc was effective in GITR(+/+) but not in GITR(-/-), suggesting that in this experimental model, its anti-inflammatory action was due to inhibition of GITR triggering and not to GITRL activation. In conclusion, GITR plays a role in SCI, and administration of GITR-Fc results in amelioration of SCI severity, prompting further studies on the potential anti-inflammatory properties of GITR-Fc.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Glucocorticoid-Induced...,
http://linkedlifedata.com/resource/pubmed/chemical/Inflammation Mediators,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Fusion Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Neuroprotective Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Nerve Growth Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Tumor Necrosis Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Tnfrsf18 protein, mouse
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
1521-0111
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pubmed:author |
pubmed-author:BianchiniRodolfoR,
pubmed-author:BramantiPlacidoP,
pubmed-author:CuzzocreaSalvatoreS,
pubmed-author:Di PaolaRosannaR,
pubmed-author:EspositoEmanuelaE,
pubmed-author:GenoveseTizianaT,
pubmed-author:MazzonEmanuelaE,
pubmed-author:NocentiniGiuseppeG,
pubmed-author:RiccardiCarloC,
pubmed-author:RonchettiSimonaS
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pubmed:issnType |
Electronic
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pubmed:volume |
73
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1610-21
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:18322000-Animals,
pubmed-meshheading:18322000-Cells, Cultured,
pubmed-meshheading:18322000-Glucocorticoid-Induced TNFR-Related Protein,
pubmed-meshheading:18322000-Inflammation,
pubmed-meshheading:18322000-Inflammation Mediators,
pubmed-meshheading:18322000-Membrane Fusion Proteins,
pubmed-meshheading:18322000-Mice,
pubmed-meshheading:18322000-Mice, Mutant Strains,
pubmed-meshheading:18322000-Neuroprotective Agents,
pubmed-meshheading:18322000-Receptors, Nerve Growth Factor,
pubmed-meshheading:18322000-Receptors, Tumor Necrosis Factor,
pubmed-meshheading:18322000-Spinal Cord Injuries,
pubmed-meshheading:18322000-Time Factors
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pubmed:year |
2008
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pubmed:articleTitle |
Glucocorticoid-induced tumor necrosis factor receptor-related (GITR)-Fc fusion protein inhibits GITR triggering and protects from the inflammatory response after spinal cord injury.
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pubmed:affiliation |
Dipartimento di Medicina Clinica e Sperimentale, Sezione di Farmacologia, Tossicologia e Chemioterapia, Università di Perugia, Italy.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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