Alpha-Melanocyte-stimulating hormone modulates lipopolysaccharide plus interferon-gamma-induced tumor necrosis factor-alpha expression but not tumor necrosis factor-alpha receptor expression in cultured hypothalamic neurons.

C. CARUSO; M. SANCHEZ; D. DURAND; M. C. PEREZ; P. V. GONZALEZ; M. LASAGA; T. SCIMONELLI

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 (alpha-MSH) exerts anti-inflammatory action through melanocortin 4 receptor (MC4R) in vivo in rat hypothalamus. In thiswork, we examined the effect of alpha-MSH on the expression of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) and their receptors in primary cultured rat hypothalamic neurons. We also investigated alpha-MSH´s possible mechanism/s of action. alpha-MSH (5 μM) decreased TNF-alpha expression induced by 24 h administration of a combination of bacterial lipopolysaccharide (LPS, 1 μg/ml) plus interferon-gamma (IFN-gamma, 50 ng/ml). Expression of TNF-alpha and IL-1beta receptors TNFR1, TNFR2 and IL-1RI, was up-regulated by LPS+IFN-gama whereas alpha-MSH did not modify basal or LPS+IFN-gamma-induced-TNFRs or IL-1RI expression. Both alpha-MSH and LPS+IFN-gamma treatments increased CREB activation. alpha-MSH did not modify NF-kB activation induced by LPS+IFN-gama in hypothalamic neurons. In conclusion, our data show that alpha-MSH reduces TNF-alpha expression in hypothalamic neurons by a mechanism which could be mediated by CREB. The regulation of inflammatory processes in the hypothalamus by alpha-MSH might help to prevent neurodegeneration resulting from inflammation.