Inhibition of peripheral NF-κB activation by central action of α- melanocyte-stimulating hormone

Takashi Ichiyama, Tetsuhiro Sakai, Anna Catania, Gregory S. Barsh, Susumu Furukawa, James M. Lipton

Research output: Contribution to journalArticle

Abstract

With the rise in the field of neuroimmunomodulation research, there is increased recognition of the influence of the nervous system and neuropeptides in peripheral disease. The neuropeptide α-melanocyte- stimulating hormone (α-MSH) is a neuroimmunomodulatory agent that modulates production of proinflammatory cytokines and inhibits peripheral inflammation via actions on CNS receptors. We examined whether central α-MSH operates by inhibiting activation of the nuclear factor kappa B (NF-κB) that is essential to the expression of proinflammatory cytokines and development of inflammation in the periphery. Electrophoretic mobility shift assays of nuclear extracts from the murine foot pad injected with TNF-α demonstrated that centrally administered α-MSH does inhibit NF-κB activation. Western blot analysis revealed that this inhibition was linked to central α-MSH- induced preservation of expression of IκBα protein in the peripheral tissue. The NF-κB and IκBα effects were inhibited in mice with spinal cord transection. Intraperitoneal (ip) injection of the nonspecific β-adrenergic receptor blocker propranolol, and of a specific β2-adrenergic receptor antagonist, likewise prevented these effects of central α-MSH; blockade of cholinergic, α-adrenergic, or β1-adrenergic receptors did not. Centrally administered α-MSH inhibited peripheral NF-κB activation and IκBα degradation even in mice with nonfunctional melanocortin 1 receptors (MC1R). These findings indicate that α-MSH can act centrally to inhibit NF-κB activation in peripheral acute inflammation via a descending neural pathway. The pathway involves β2-adrenergic receptors, but does not require activation of MC1R within the brain.

Original languageEnglish
Pages (from-to)211-217
Number of pages7
JournalJournal of Neuroimmunology
Volume99
Issue number2
DOIs
Publication statusPublished - Oct 29 1999

Keywords

  • α-Melanocyte-stimulating hormone
  • β-Adrenoreceptor
  • Inflammation
  • Melanocortin receptor
  • NF-κB
  • Spinal cord transection

ASJC Scopus subject areas

  • Immunology
  • Clinical Neurology
  • Immunology and Allergy
  • Neurology

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