Systemically administered alpha-melanocyte-stimulating peptides inhibit NF-kappa B activation in experimental brain inflammation

The neuropeptide alpha-melanocyte-stimulating hormone (alpha-MSH) and its C -terminal tripeptide alpha-MSH11-13 modulate production of proinflammatory cytokines and inhibit inflammation. We examined whether systemic alpha-MSH and alpha-MSH11-13 inhibit activation of the nuclear transcription factor, nuclear factor kappa B (NF-kappa B), a factor that is essential to expressi on of proinflammatory cytokines, in experimental murine brain inflammation induced by lipopolysaccharide. Electrophoretic mobility shift assays of nuc lear extracts demonstrated that parenteral alpha-MSH inhibited NF-kappa B a ctivation. Western blot analysis revealed that this inhibition was linked t o alpha-MSH-induced preservation of expression of I kappa B alpha protein i n the brain. The effects of alpha-MSH on NF-kappa B and I kappa B alpha wer e paralleled by pretreatment with alpha-MSH11-13. Similar effects of the tw o peptides were observed in mice with nonfunctional melanocortin 1 receptor s (MC1R), ruling out the possibility that this receptor subtype is essentia l to the influence on NF-kappa B. These findings indicate that alpha-MSH pe ptides given systemically can inhibit NF-kappa B activation induced in acut e brain inflammation even in the absence of MC1R. (C) 1999 Elsevier Science B.V. All rights reserved.