Systemically administered α-melanocyte-stimulating peptides inhibit NF-κB activation in experimental brain inflammation

Abstract The neuropeptide α-melanocyte-stimulating hormone (α-MSH) and its C-terminal tripeptide α-MSH11-13 modulate production of proinflammatory cytokines and inhibit inflammation. We examined whether systemic α-MSH and α-MSH11-13 inhibit activation of the nuclear transcription factor, nuclear factor kappa B (NF-κB), a factor that is essential to expression of proinflammatory cytokines, in experimental murine brain inflammation induced by lipopolysaccharide. Electrophoretic mobility shift assays of nuclear extracts demonstrated that parenteral α-MSH inhibited NF-κB activation. Western blot analysis revealed that this inhibition was linked to α-MSH-induced preservation of expression of IκBα protein in the brain. The effects of α-MSH on NF-κB and IκBα were paralleled by pretreatment with α-MSH11-13. Similar effects of the two peptides were observed in mice with nonfunctional melanocortin 1 receptors (MC1R), ruling out the possibility that this receptor subtype is essential to the influence on NF-κB. These findings indicate that α-MSH peptides given systemically can inhibit NF-κB activation induced in acute brain inflammation even in the absence of MC1R.