α-MSH Peptides Inhibit Production of Nitric Oxide and Tumor Necrosis Factor-α by Microglial Cells Activated with β-Amyloid and Interferon γ

• Published in: Biochemical and biophysical research communications 1999-09, Vol.263 (1), p.251-256
• Main Authors: Galimberti, Daniela, Baron, Pierluigi, Meda, Lucia, Prat, Elisabetta, Scarpini, Elio, Delgado, René, Catania, Anna, Lipton, James M., Scarlato, Guglielmo
• Format: Article
• Language: English
• Subjects: a-Melanocyte-stimulating hormone; alpha-MSH - pharmacology; Amyloid beta-Peptides - pharmacology; Animals; Cell Line; Inflammation Mediators - metabolism; Interferon-gamma - pharmacology; Melanocyte-Stimulating Hormones - pharmacology; Mice; Microglia - drug effects; Microglia - metabolism; Nitric Oxide - biosynthesis; Nitric Oxide Synthase - genetics; Nitric Oxide Synthase - metabolism; Nitric Oxide Synthase Type II; Peptide Fragments - pharmacology; Recombinant Proteins; RNA, Messenger - genetics; RNA, Messenger - metabolism; Tumor Necrosis Factor-alpha - biosynthesis; Tumor Necrosis Factor-alpha - genetics
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1006/bbrc.1999.1276

α-Melanocyte stimulating hormone (α-MSH) is an ancient tridecapeptide with potent inhibitory activity in all major forms of inflammation. The anti-inflammatory message sequence of α-MSH resides in the COOH-terminal tripeptide α-MSH[11–13]. We tested the influence of α-MSH[1–13] and of α-MSH[11–13] in a cultured murine microglia cell line known to produce nitric oxide (NO−2) and tumor necrosis factor (TNFα) when stimulated with β-amyloid protein (Aβ). Melanocortin peptides significantly inhibited release of both NO−2 and TNFα into cell-free supernatants from microglia stimulated with Aβ[1–42] or Aβ[25–35] peptides and interferon γ (IFNγ). Northern blot analysis demonstrated that α-MSH[1–13] and α-MSH[11–13] inhibited accumulation of inducible nitric oxide synthase (iNOS) and TNFα mRNA was triggered by Aβ stimulation. Aβ/microglial interaction is believed to promote the progression of inflammatory and neurodegenerative changes in senile plaques in Alzheimer's disease. Our data indicate that α-MSH peptides might be used to modulate the local response of the brain to Aβ deposition in this neurodegenerative disease.