alpha-Melanocyte-stimulating hormone modulates lipopolysaccharide plus

CARUSO C, ; SANCHEZ M; DURAND D; DE LA CRUZ PEREZ M; GONZALEZ P; LASAGA M; SCIMONELLI T

JOURNAL OF NEUROIMMUNOLOGY

ELSEVIER SCIENCE BV

Año: 2010 vol. 227 p. 52 - 59

0165-5728

In a previous work we showed that the melanocortin alpha-melanocyte stimulating hormone (a-MSH) exerts anti-inflammatory action through melanocortin receptor 4 (MC4R) in rat hypothalamus. In this work, we examined the effect of a-MSH on the expression of tumour necrosis factor-a (TNF-a) and interleukin-1b (IL-1b) and their receptors in primary cultured rat hypothalamic neurons. We also investigated a-MSH´s possible mechanism/s of action. a-MSH (5 mM) decreased TNF-a expression induced by 24 h treatment with the combination of bacterial lipopolysaccharide (LPS, 1 mg/ml) plus interferon-g (IFN-g, 50 ng/ml). Expression of TNF-a and IL-1b receptors TNFR1, TNFR2 and IL-1RI, was up-regulated by LPS+IFN-g whereas a-MSH did not modify TNFRs or IL-1RI basal or LPS+IFN-g-induced expression. Both a-MSH and LPS+IFN-g treatments increased CREB activation. a-MSH did not modify NF-kB activation induced by LPS+IFN-g in hypothalamic neurons.In conclusion, our data show that a-MSH reduces TNF-a expression in hypothalamic neurons by a mechanism which could be mediated by CREB. The regulation of inflammatory processes in the hypothalamus by a-MSH might help to prevent neurodegeneration as a consequence of inflammation.