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