alpha-melanocyte-stimulating hormone inhibits NF-kappaB activation and IkappaBalpha degradation in human glioma cells and in experimental brain inflammation

Exp Neurol. 1999 Jun;157(2):359-65. doi: 10.1006/exnr.1999.7064.


The neuropeptide alpha-melanocyte-stimulating hormone (alpha-MSH) modulates production of proinflammatory cytokines in brain tissue and in peripheral inflammatory cells. Transcription of the genes for these proinflammatory cytokines is regulated by the nuclear factor kappaB (NF-kappaB). NF-kappaB is also activated by proinflammatory cytokines. Degradation of the cytoplasmic inhibitor IkappaBalpha protein results in activation of NF-kappaB. Because of increasing evidence that NF-kappaB is involved in brain injury and inflammation and neurodegenerative disease, we examined whether alpha-MSH inhibits activation of NF-kappaB and limits degradation of IkappaBalpha protein induced by lipopolysaccharide (LPS) in human glioma cells (A-172) and in mouse brain. Electrophoretic mobility shift assays of nuclear extracts from A-172 cells and whole mouse brains stimulated with LPS revealed that alpha-MSH does suppress NF-kappaB activation. Western blot analysis demonstrated that alpha-MSH preserved expression of IkappaBalpha protein in vitro (glioma cells) and in vivo (brain tissue). Chloramphenicol acetyltransferase assay indicated that alpha-MSH suppresses NF-kappaB-dependent reporter gene expression induced by LPS in A-172 cells. The findings are consistent with the possibility that the anti-inflammatory action of alpha-MSH in CNS inflammation occurs via modulation of NF-kappaB activation by peptide-induced inhibition of degradation of IkappaBalpha protein.

MeSH terms

  • Animals
  • Brain / metabolism*
  • Brain / pathology
  • Cell Nucleus / drug effects
  • Cell Nucleus / metabolism
  • Chloramphenicol O-Acetyltransferase / genetics
  • Cytokines / genetics
  • DNA-Binding Proteins / metabolism*
  • Gene Expression Regulation / drug effects*
  • Gene Expression Regulation, Neoplastic / drug effects
  • Glioma
  • Humans
  • I-kappa B Proteins*
  • Inflammation
  • Kinetics
  • Lipopolysaccharides / toxicity
  • Male
  • Mice
  • Mice, Inbred BALB C
  • NF-KappaB Inhibitor alpha
  • NF-kappa B / antagonists & inhibitors
  • NF-kappa B / metabolism*
  • Transcription, Genetic
  • Transfection
  • Tumor Cells, Cultured
  • alpha-MSH / pharmacology*


  • Cytokines
  • DNA-Binding Proteins
  • I-kappa B Proteins
  • Lipopolysaccharides
  • NF-kappa B
  • NFKBIA protein, human
  • Nfkbia protein, mouse
  • NF-KappaB Inhibitor alpha
  • alpha-MSH
  • Chloramphenicol O-Acetyltransferase