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

Brain Res. 1999 Jul 31;836(1-2):31-7. doi: 10.1016/s0006-8993(99)01584-x.


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-kappaB), 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 alpha-MSH inhibited NF-kappaB activation. Western blot analysis revealed that this inhibition was linked to alpha-MSH-induced preservation of expression of IkappaBalpha protein in the brain. The effects of alpha-MSH on NF-kappaB and IkappaBalpha were paralleled by pretreatment with alpha-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-kappaB. These findings indicate that alpha-MSH peptides given systemically can inhibit NF-kappaB activation induced in acute brain inflammation even in the absence of MC1R.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Brain Diseases / chemically induced
  • Brain Diseases / drug therapy*
  • Cytokines / biosynthesis
  • Injections, Intraventricular
  • Lipopolysaccharides / toxicity
  • Male
  • Mice
  • Mice, Inbred C57BL
  • NF-kappa B / antagonists & inhibitors*
  • Neuritis / chemically induced
  • Neuritis / drug therapy*
  • alpha-MSH / therapeutic use*


  • Cytokines
  • Lipopolysaccharides
  • NF-kappa B
  • alpha-MSH