Binding of anti-inflammatory a-melanocyte-stimulating-hormone peptides and proinflammatory cytokines to receptors on melanoma cells

Krzysztof Lyson, Giuliana Ceriani, Akira Takashima, Anna Catania, James M. Lipton

Research output: Contribution to journalArticle

Abstract

α-Melanocyte-stimulating hormone (α-MSH1-13), a peptide derived from proopiomelanocortin, has remarkable anti-inflammatory and antipyretic activities. This peptide and a tripeptide that forms the COOH-terminal portion of the molecule (α-MSH11-13; Lys Pro Val) inhibit inflammation when given centrally or peripherally. Because of the similarity in their actions, the tripeptide has been presumed to be the amino acid message sequence underlying the effects of α-MSH1-13. To test the possibility that the two peptides occupy the same receptors, competitive binding experiments were performed with B16 mouse melanoma cells that are known to have α-MSH1-13 receptors. In these experiments, α-MSH11-13 did not inhibit binding of a radiolabelled α-MSH1-13 analog. This finding suggests that α-MSH1-13 and α-MSH11-13 exert their anti- inflammatory/antipyretic/anticytokine effects via stimulation of separate receptors. Because α-MSH inhibits the effects of several cytokines including inflammation caused by interleukin (IL)-6 and IL-8, the capacity of these cytokines to compete for α-MSH binding sites was tested. There was no evidence that these proinflammatory cytokines bind to α-MSH receptors on murine melanoma cells. Although further tests with host cells involved in inflammation are required, the latter result is the first evidence that the mechanism of anticytokine action of α-MSH does not depend upon peptide/cytokine competition for binding sites.

Original languageEnglish
Pages (from-to)121-126
Number of pages6
JournalNeuroImmunoModulation
Volume1
Issue number2
DOIs
Publication statusPublished - 1994

Keywords

  • Competitive binding
  • Interleukin-6
  • Interleukin-8
  • Melanocytes
  • Saturation binding
  • α-MSH analog
  • α-MSH<inf>1-13</inf> receptors
  • α-MSH<inf>11-13</inf> receptors

ASJC Scopus subject areas

  • Endocrinology
  • Immunology
  • Endocrine and Autonomic Systems
  • Neurology
  • Neuroscience(all)

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