SCIMONELLI TERESA NIEVES
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Congresos y reuniones científicas
Título:
a-MSH modulates TNF-a and IL-1b expression in cultured astrocytes and neurons.
Autor/es:
CARUSO C,; PEREZ M; DURAND D; SANCHEZ M; SCIMONELLI T; LASAGA M
Lugar:
Toronto,
Reunión:
Congreso; 89th Annual Meeting of the Endocrine Society; 2007
Institución organizadora:
The Endocrine Society
Resumen:
Inflammatory mediators such as cytokines (e.g. TNF-a and IL1-b) and nitric oxide (NO) are increased in neurodegenerative diseases suggesting that these factors can contribute to neural damage. a-melanocyte stimulating hormone (a-MSH) is a melanocortin that has systemic and central anti-inflammatory properties. We previously demonstrated that a-MSH can reduced hypothalamic NO and prostaglandins production induced by lipopolysaccharide (LPS) through melanocortin receptor 4 (MC4R) (1). Since astrocytes and neurons have different responses to pro-inflammatory stimuli and express melanocortin receptors, we investigated the effect of LPS (1 ug/ml) + IFN-g (50 ng/ml) and a-MSH (5 uM) on the gene expression of TNF-a and its receptors (TNFR1 and TNFR2) in cultured rat astrocytes and hypothalamic neurons (determined by RT-PCR).
In astrocytes, mRNA levels of TNF-a and TNFR2 were increased by LPS+IFN-g treatment whereas TNFR1 levels were not modified after 24 h. a-MSH per se did not modify TNF-a , TNFR1 or TNFR2 expression. However, this melanocortin significantly attenuated the increase in the expression of TNF-a induced by LPS+IFN-g by 40% ( p< 0.05) whereas it had no effect on TNFR2 gene expression. This anti-inflammatory effect was not observed in the presence of a selective MC4R antagonist (HS024, 0.5 uM).
In hypothalamic neurons, mRNA levels of TNF-a , TNFR1 and TNFR2 were increased by LPS+IFN- treatment after 24 h. Again, a-MSH reduced TNF-a expression induced by LPS+IFN-g in these cells by 45% ( p< 0.05) whereas per se had no effect.
We also investigated the expression of IL-1 and IL-1 receptor 1 (IL-1R1) in astrocytes. IL-1 and IL-1R1 mRNA levels were significantly increased by LPS+ IFN-a treatment by 4 fold and 2 fold respectively. a-MSH attenuated IL-1 and IL-1R1 expression induced by LPS+IFN- by 20 % and 43% respectively (p<0.05) . Treatment with the selective MC4R antagonist prevented the inhibitory effect of the neuropeptide.
These data suggest that a-MSH has an anti-inflammatory effect by attenuating TNF-a expression induced by LPS+INF-g in hypothalamic neurons and astrocytes in culture. Moreover, this melanocortin also decreased the stimulatory effect of LPS+INF-g on IL-1 and IL-1R1 gene expression in astrocytes. The anti-inflamatory action of a-MSH may be exerted via MC4 receptors.


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