There is evidence that the melanocortin alpha-melanocyte stimulating hormone (a-MSH) has immunomodulatory and anti-inflammatory actions within the brain. The aim of the present study was to establish the effect of a-MSH on LPS+IFN-g-induced signalling pathways in hypothalamic neurones or astrocytes in culture. We found that a-MSH suppresses LPS+IFN-g- induced nuclear translocation of the transcription factor NF-kB. Besides, treatment with LPS+IFN-g stimulates phosphorylation of cAMP-responsive element-binding protein (CREB), but this effect was not modified by a-MSH. In neurones, LPS+IFN-g elicited a slight increase in CREB activation. Treatment with a-MSH induced CREB phosphorylation and the combination of LPS+IFN-g and a-MSH induced an additive increase in CREB activation. Our results demonstrated that a-MSH can differently modulate signalling transduction pathways induced by LPS+IFN-g.
