α-Melanocyte-stimulating hormone inhibits NF-κB activation and IκBα degradation in human glioma cells and in experimental brain inflammation

Takashi Ichiyama, Hui Zhao, Anna Catania, Susumu Furukawa, James M. Lipton

Research output: Contribution to journalArticle

Abstract

The neuropeptide α-melanocyte-stimulating hormone (α-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 κB (NF-κB). NF-κB is also activated by proinflammatory cytokines. Degradation of the cytoplasmic inhibitor IκBα protein results in activation of NF-κB. Because of increasing evidence that NF-κB is involved in brain injury and inflammation and neurodegenerative disease, we examined whether α-MSH inhibits activation of NF-κB and limits degradation of IκBα 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 α-MSH does suppress NF-κB activation. Western blot analysis demonstrated that α-MSH preserved expression of IκBα protein in vitro (glioma cells) and in vivo (brain tissue). Chloramphenicol acetyltransferase assay indicated that α-MSH suppresses NF-κB-dependent reporter gene expression induced by LPS in A-172 cells. The findings are consistent with the possibility that the anti- inflammatory action of α-MSH in CNS inflammation occurs via modulation of NF-κB activation by peptide-induced inhibition of degradation of IκBα protein.

Original languageEnglish
Pages (from-to)359-365
Number of pages7
JournalExperimental Neurology
Volume157
Issue number2
DOIs
Publication statusPublished - Jun 1999

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Keywords

  • α-Melanocyte-stimulating hormone
  • Astrocyte
  • Inflammation
  • Lipopolysaccharide
  • NF-κB; IκBα

ASJC Scopus subject areas

  • Neurology
  • Neuroscience(all)

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