Artículo
Activation of melanocortin 4 receptors reduces the inflammatory response and prevents apoptosis induced by lipopolysaccharide and interferon-γ in astrocytes
Caruso, Carla Mariana
; Durand, Daniela Elizabeth
; Schiöth, Helgi Birgir; Rey, Rodolfo Alberto
; Seilicovich, Adriana
; Lasaga, Mercedes Isabel
Fecha de publicación:
10/2007
Editorial:
Endocrine Society
Revista:
Endocrinology
ISSN:
0013-7227
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
α-MSH exerts an immunomodulatory action in the brain and may play a neuroprotective role acting through melanocortin 4 receptors (MC4Rs). In the present study, we show that MC4Rs are constitutively expressed in astrocytes as determined by immunocytochemistry, RT-PCR, and Western blot analysis. α-MSH (5 μM) reduced the nitric oxide production and the expression of inducible nitric oxide synthase (iNOS) induced by bacterial lipopolysaccharide (LPS, 1 μg/ml) plus interferon-γ (IFN-γ, 50 ng/ml) in cultured astrocytes after 24 h. α-MSH also attenuated the stimulatory effect of LPS/IFN-γ on prostaglandin E2 release and cyclooxygenase-2 (COX-2) expression. Treatment with HS024, a selective MC4R antagonist, blocked the antiinflammatory effects of α-MSH, suggesting a MC4R-mediated mechanism in the action of this melanocortin. In astrocytes, LPS/IFN-γ treatment reduced cell viability, increased the number of terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling-positive cells and activated caspase-3. α-MSH prevented these apoptotic events, and this cytoprotective effect was abolished by HS024. LPS/IFN-γ decreased Bcl-2, whereas it increased Bax protein expression in astrocytes, thus increasing the Bax/Bcl-2 ratio. α-MSH produced a shift in Bax/Bcl-2 ratio toward astrocyte survival because it increased Bcl-2 expression and also prevented the effect of LPS/IFN-γ on Bax and Bcl-2 expression. In summary, these findings suggest that α-MSH, through MC4R activation, attenuates LPS/IFN-γ-induced inflammation by decreasing iNOS and COX-2 expression and prevents LPS/ IFN-γ-induced apoptosis of astrocytes by modulating the expression of proteins of the Bcl-2 family.
Palabras clave:
MC4 RECEPTOR
,
ASTROCYTES
,
INFLAMMATION
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Colecciones
Articulos(CEDIE)
Articulos de CENTRO DE INVESTIGACIONES ENDOCRINOLOGICAS "DR. CESAR BERGADA"
Articulos de CENTRO DE INVESTIGACIONES ENDOCRINOLOGICAS "DR. CESAR BERGADA"
Articulos(INBIOMED)
Articulos de INSTITUTO DE INVESTIGACIONES BIOMEDICAS
Articulos de INSTITUTO DE INVESTIGACIONES BIOMEDICAS
Articulos(OCA HOUSSAY)
Articulos de OFICINA DE COORDINACION ADMINISTRATIVA HOUSSAY
Articulos de OFICINA DE COORDINACION ADMINISTRATIVA HOUSSAY
Citación
Caruso, Carla Mariana; Durand, Daniela Elizabeth; Schiöth, Helgi Birgir; Rey, Rodolfo Alberto; Seilicovich, Adriana; et al.; Activation of melanocortin 4 receptors reduces the inflammatory response and prevents apoptosis induced by lipopolysaccharide and interferon-γ in astrocytes; Endocrine Society; Endocrinology; 148; 10; 10-2007; 4918-4926
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