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Gewählte Publikation:

Publikationstyp: Zeitschriftenaufsatz
Dokumenttyp: Originalarbeit

Jahr: 2008

AutorInnen: Nocentini, G; Cuzzocrea, S; Genovese, T; Bianchini, R; Mazzon, E; Ronchetti, S; Esposito, E; Rosanna, DP; Bramanti, P; Riccardi, C

Titel: Glucocorticoid-induced tumor necrosis factor receptor-related (GITR)-Fc fusion protein inhibits GITR triggering and protects from the inflammatory response after spinal cord injury.

Quelle: Mol Pharmacol. 2008; 73(6):1610-21



Autor/innen der Vetmeduni Vienna:

Bianchini Rodolfo

Diese Publikation wurde nicht im Namen der Vetmeduni Vienna erstellt und ist deshalb ausschließlich der persönlichen Publikationsliste des/der Autors/Autorin zugeordnet!


Abstract:
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.

Keywords Pubmed: Animals
Cells, Cultured
Glucocorticoid-Induced TNFR-Related Protein
Inflammationimmunologymetabolismprevention & control
Inflammation Mediatorsmetabolismtherapeutic use
Membrane Fusion Proteinsgeneticsmetabolismtherapeutic use
Mice
Mice, Mutant Strains
Neuroprotective Agentsmetabolismtherapeutic use
Receptors, Nerve Growth Factordeficiencygeneticstherapeutic use
Receptors, Tumor Necrosis Factordeficiencygeneticstherapeutic use
Spinal Cord Injuriesimmunologymetabolismprevention & control
Time Factors

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