CEFYBO   02669
CENTRO DE ESTUDIOS FARMACOLOGICOS Y BOTANICOS
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Participation of endocannabinoid system on TNF-alpha release from rat astrocytes after LPS
Autor/es:
LUCE V; CARUSO C; CARNIGLIA L; LASAGA M; RETTORI V; DE LAURENTIIS A
Lugar:
San Petesburgo
Reunión:
Simposio; III International Symposium : Interactions of the nervous and immune systems in heallth and disease; 2011
Institución organizadora:
Institute of Experimental Medicine, Rusia
Resumen:
It is known, that in response to several
stimuli like bacterial endotoxins, astrocytes release proinflammatory
mediators, such us TNF-alpha, which may play an important role in eliciting
neuroinflammatory processes causing brain damage. Since cannabinoids have been
reported to exert anti-inflammatory and neuroprotective actions in the brain,
we examined the participation of the endogenous cannabinoid system on TNF-alpha
release elicited by bacterial endotoxin lipopolysaccharide (LPS) in combination
with interferon gamma (INF) in primary cultured rat astrocytes. Exposure of cultured
astrocytes to LPS (1ug/ml) + INF (50ng/ml) during 90 min, 4 h and 24 hs significantly
stimulated (p<0.001) TNF-alpha concentration in supernatants, determined by
ELISA. CB1 and CB2 receptors are expressed by astrocytes and their activation by
cannabinoid compounds regulates these cells functions. The presence of CB2
receptor antagonist (AM630, 10-5M) blocked the stimulatory effect of
LPS+INF on TNF-alpha release, while CB1 antagonist (AM251, 10-5M)
had no effect. The addition of the synthetic cannabinoid methanandamide
(MetAEA, 10-9M) significantly decreased (p<0.01) basal TNF-alpha
release but had a slight stimulatory effect on LPS-induced TNF-alpha release.
Also, the addition of a fatty acid amide hydrolase inhibitor (URB597, 1uM) that
increases endogenous anandamide levels, significantly decreased (p<0.01) basal
TNF-alpha release and slightly decreased LPS-induced TNF-alpha levels.
Taken together, these observations indicate that
the endocannabinoid system modulates the release of TNF-alpha from astrocytes
in culture and that the main effect appears to be mediated by CB2 receptors.