Melanocortin peptides inhibit production of proinflammatory cytokines and nitric oxide by activated microglia

René Delgado, Andrea Carlin, Lorena Airaghi, Maria Teresa Demitri, Lucia Meda, Daniela Galimberti, Pierluigi Baron, James M. Lipton, Anna Catania

Research output: Contribution to journalArticlepeer-review

Abstract

Inflammatory processes contribute to neurodegenerative disease, stroke, encephalitis, and other central nervous system (CNS) disorders. Activated microglia are a source of cytokines and other inflammatory agents within the CNS and it is therefore important to control glial function in order to preserve neural cells. Melanocortin peptides are pro-opiomelanocortin- derived amino acid sequences that include α-melanocyte-stimulating hormone (α-MSH) and adrenocorticotropic hormone (ACTH). These peptides have potent and broad anti-inflammatory effects. We tested effects of α-MSH (1-13), α- MSH (11-13), and ACTH (1-24) on production of tumor necrosis factor α (TNF- α), interleukin-6 (IL-6), and nitric oxide (NO) in a cultured murine microglial cell line (N9) stimulated with lipopolysaccharide (LPS) plus interferon γ (IFN-γ). Melanocortin peptides inhibited production of these cytokines and NO in a concentration-related fashion, probably by increasing intracellular cAMP. When stimulated with LPS + IFN-γ, microglia increased release of α-MSH. Production of TNF-α, IL-6, and NO was greater in activated microglia after immunoneutralization of endogenous α-MSH. The results suggest that α-MSH is an autocrine factor in microglia. Because melanocortin peptides inhibit production of pro-inflammatory mediators by activated microglia they might be useful in treatment of inflammatory/degenerative brain disorders.

Original languageEnglish
Pages (from-to)740-745
Number of pages6
JournalJournal of Leukocyte Biology
Volume63
Issue number6
Publication statusPublished - Jun 1998

Keywords

  • α-melanocyte-stimulating hormone
  • Adrenocorticotropic hormone
  • Cyclic AMP
  • Interleukin-6
  • Tumor necrosis factor

ASJC Scopus subject areas

  • Cell Biology

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