Insulin-like growth factor-I gene delivery to astrocytes reduces their inflammatory response to lipopolysaccharide

Background: Insulin-like growth factor-I (IGF-I) exerts neuroprotective actions in the central nervous system that are mediated at least in part by control of activation of astrocytes. In this study we have assessed the efficacy of exogenous IGF-I and IGF-I gene therapy in reducing the inflammatory...

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Autores principales:	Bellini, María José, Hereñú, Claudia Beatriz, Goya, Rodolfo Gustavo, García Segura, Luis M.
Formato:	Articulo
Lenguaje:	Inglés
Publicado:	2011
Materias:	Ciencias Médicas adenovirus vector neuroprotection genetics immunology metabolism physiology
Acceso en línea:	http://sedici.unlp.edu.ar/handle/10915/37663 http://www.jneuroinflammation.com/content/pdf/1742-2094-8-21.pdf
Aporte de:	SEDICI (UNLP) de Universidad Nacional de La Plata

id	I19-R120-10915-37663
record_format	dspace
institution	Universidad Nacional de La Plata
institution_str	I-19
repository_str	R-120
collection	SEDICI (UNLP)
language	Inglés
topic	Ciencias Médicas adenovirus vector neuroprotection genetics immunology metabolism physiology
spellingShingle	Ciencias Médicas adenovirus vector neuroprotection genetics immunology metabolism physiology Bellini, María José Hereñú, Claudia Beatriz Goya, Rodolfo Gustavo García Segura, Luis M. Insulin-like growth factor-I gene delivery to astrocytes reduces their inflammatory response to lipopolysaccharide
topic_facet	Ciencias Médicas adenovirus vector neuroprotection genetics immunology metabolism physiology
description	Background: Insulin-like growth factor-I (IGF-I) exerts neuroprotective actions in the central nervous system that are mediated at least in part by control of activation of astrocytes. In this study we have assessed the efficacy of exogenous IGF-I and IGF-I gene therapy in reducing the inflammatory response of astrocytes from cerebral cortex. Methods: An adenoviral vector harboring the rat IGF-I gene and a control adenoviral vector harboring a hybrid gene encoding the herpes simplex virus type 1 thymidine kinase fused to Aequorea victoria enhanced green fluorescent protein were used in this study. Primary astrocytes from mice cerebral cortex were incubated for 24 h or 72 h with vehicle, IGF-I, the IGF-I adenoviral vector, or control vector; and exposed to bacterial lipopolysaccharide to induce an inflammatory response. IGF-I levels were measured by radioimmunoassay. Levels of interleukin 6, tumor necrosis factor-α, interleukin-1β and toll-like receptor 4 mRNA were assessed by quantitative real-time polymerase chain reaction. Levels of IGF-I receptor and IGF binding proteins 2 and 3 were assessed by western blotting. The subcellular distribution of nuclear factor κB (p65) was assessed by immunocytochemistry. Statistical significance was assessed by one way analysis of variance followed by the Bonferroni pot hoc test. Results: IGF-I gene therapy increased IGF-I levels without affecting IGF-I receptors or IGF binding proteins. Exogenous IGF-I, and IGF-I gene therapy, decreased expression of toll-like receptor 4 and counteracted the lipopolysaccharide-induced inflammatory response of astrocytes. In addition, IGF-I gene therapy decreased lipopolysaccharide-induced translocation of nuclear factor κB (p65) to the cell nucleus. Conclusion: These findings demonstrate efficacy of exogenous IGF-I and of IGF-I gene therapy in reducing the inflammatory response of astrocytes. IGF-I gene therapy may represent a new approach to reduce inflammatory reactions in glial cells.
format	Articulo Articulo
author	Bellini, María José Hereñú, Claudia Beatriz Goya, Rodolfo Gustavo García Segura, Luis M.
author_facet	Bellini, María José Hereñú, Claudia Beatriz Goya, Rodolfo Gustavo García Segura, Luis M.
author_sort	Bellini, María José
title	Insulin-like growth factor-I gene delivery to astrocytes reduces their inflammatory response to lipopolysaccharide
title_short	Insulin-like growth factor-I gene delivery to astrocytes reduces their inflammatory response to lipopolysaccharide
title_full	Insulin-like growth factor-I gene delivery to astrocytes reduces their inflammatory response to lipopolysaccharide
title_fullStr	Insulin-like growth factor-I gene delivery to astrocytes reduces their inflammatory response to lipopolysaccharide
title_full_unstemmed	Insulin-like growth factor-I gene delivery to astrocytes reduces their inflammatory response to lipopolysaccharide
title_sort	insulin-like growth factor-i gene delivery to astrocytes reduces their inflammatory response to lipopolysaccharide
publishDate	2011
url	http://sedici.unlp.edu.ar/handle/10915/37663 http://www.jneuroinflammation.com/content/pdf/1742-2094-8-21.pdf
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bdutipo_str	Repositorios
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Insulin-like growth factor-I gene delivery to astrocytes reduces their inflammatory response to lipopolysaccharide

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