INV SUPERIOR JUBILADO
SEILICOVICH Adriana
congresos y reuniones científicas
Título:
Modulatory role of alpha-MSH on pro-inflammatory and pro-apoptotic effects induced by LPS + INF gamma in astrocytes
Autor/es:
CARUSO C; DURAND D; SCHIOTH HB; SEILICOVICH A; LASAGA M
Reunión:
Congreso; 35th. Annual Meeting of the Society for Neuroscience; 2005
Resumen:
There is evidence that alpha-melanocyte-stimulating hormone (alpha-MSH) has immunomodulatory and anti-inflammatory actions within the brain. We have previously demonstrated that alpha-MSH reduces the increase of iNOS and COX-2 gene expression at the hypothalamic level induced by lipopolysaccharide (LPS) and suggest that endogenous alpha-MSH may exert an inhibitory tone on iNOS and COX-2 transcription via MC4 receptors acting as a local anti-inflammatory agent within the hypothalamus. Since astrocytes are pivotal in the modulation of inflammation of the CNS, in the present study we studied a possible role of alpha-MSH in inducible nitric oxide synthase (iNOS) gene expression and nitric oxide (NO) production after LPS (1ug/ml)/ interferon-gamma (IFN gamma) (50 ng/ml) treatment in primary rat astrocytes in culture. We found that LPS/IFN-gamma after 24 hs exposure significantly increased NO production and induced iNOS gene expression determined by RT-PCR. Alpha-MSH attenuated the LPS/IFN-gamma induced NO production and iNOS expression. LPS/IFN-gamma also caused a decreased in cell viability and significantly increased the number of TUNEL positive astrocytes and the activity of caspase-3 indicating that LPS/IFN-gamma induce apoptosis in astrocytes. The addition of alpha-MSH resulted in a decreased LPS/IFN-gamma-induced effects. We detected the presence of MC4 and MC3 receptors in hypothalamus male rats. mRNA expression of MC4 and MC3 receptors were analyzed by RT-PCR  while the protein levels were determined by Western Blot. When we tested the presence of these receptors in astrocytes we only found MC4 receptors.  Our previous findings in in vivo studies supported the conclusions drawn from astrocytes culture studies and provided evidence for the possible role of MC4 receptors in LPS + IFN-gamma induced inflammation and apoptosis.