SCIMONELLI TERESA NIEVES
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Título:
a-MSH modulates TNF-a and IL-1b expression in cultured astrocytes and neurons.
Autor/es:
· CARUSO C, PEREZ MC, DURAND D, SANCHEZ M, SCIMONELLI T, LASAGA M
Lugar:
Toronto, Canadá.
Reunión:
Congreso; 89th Annual Meeting of the Endocrine Society; 2007
Institución organizadora:
The Endocrine Society
Resumen:
Inflammatory mediators such as cytokines (e.g. TNF- and IL1- ) and nitric oxide (NO) are increased in neurodegenerative diseases suggesting that these factors can contribute to neural damage. a-melanocyte stimulating hormone ( -MSH) is a melanocortin that has systemic and central anti-inflammatory properties. We previously demonstrated that -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- (50 ng/ml) and -MSH (5 uM) on the gene expression of TNF- and its receptors (TNFR1 and TNFR2) in cultured rat astrocytes and hypothalamic neurons (determined by RT-PCR).
In astrocytes, mRNA levels of TNF- and TNFR2 were increased by LPS+IFN- treatment whereas TNFR1 levels were not modified after 24 h. -MSH per se did not modify TNF- , TNFR1 or TNFR2 expression. However, this melanocortin significantly attenuated the increase in the expression of TNF- induced by LPS+IFN- 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- , TNFR1 and TNFR2 were increased by LPS+IFN- treatment after 24 h. Again, -MSH reduced TNF- expression induced by LPS+IFN- 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- treatment by 4 fold and 2 fold respectively. -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 -MSH has an anti-inflammatory effect by attenuating TNF- expression induced by LPS+INF- in hypothalamic neurons and astrocytes in culture. Moreover, this melanocortin also decreased the stimulatory effect of LPS+INF- on IL-1 and IL-1R1 gene expression in astrocytes. The anti-inflamatory action of -MSH may be exerted via MC4 receptors.


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