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

作者：Caruso Carla^*; Sanchez Monica; Durand Daniela; de la Cruz Perez Maria; Gonzalez Patricia V; Lasaga Mercedes; Scimonelli Teresa N

来源：Journal of Neuroimmunology, 2010, 227(1-2): 52-59.

DOI：10.1016/j.jneuroim.2010.06.013

• alpha-MSH
• TNF-alpha
• IL-1 beta
• Hypothalamic neurons
• CREB
• NF-kappa B

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 this work, we examined the effect of alpha-MSH on the expression of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) and their receptors in primary cultured rat hypothalamic neurons. We also investigated alpha-MSH's possible mechanism/s of action. alpha-MSH (5 mu M) decreased TNF-alpha expression induced by 24 h administration of a combination of bacterial lipopolysaccharide (LPS, 1 mu g/ml) plus interferon-gamma (IFN-gamma, 50 ng/ml). Expression of TNF-alpha and IL-1 beta receptors TNFR1, TNFR2 and IL-1RI, was up-regulated by LPS + IFN-gamma 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. a-MSH did not modify NF-kappa B activation induced by LPS + IFN-gamma 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.

• 出版日期2010-10-8