A potential mechanism of local anti-inflammatory action of alpha-melanocyte-stimulating hormone within the brain: Modulation of tumor necrosis factor-alpha production by human astrocytic Cells

Kit Yue Wong, Nilum Rajora, Giovanni Boccoli, Anna Catania, James M. Lipton

Research output: Contribution to journalArticle

61 Scopus citations

Abstract

The proinflammatory cytokine tumor necrosis factor-α(TNF-α) occurs in CNS tissue in neurological disorders, infection, and injury. Its excessive production is believed to contribute to local pathology, in which case modulation of TNF-αproduction should promote survival of neural tissue. The neuropeptideα-melanocyte stimulating hormone [α-MSH (1-13)] inhibits TNF-αproduction in vivo and in vitro, and in this research we tested the capacity of the peptide, and of an anti-inflammatory COOH-terminal tripeptide fragment of it, to inhibit TNF-αproduction induced by bacterial endotoxin in cells of a human glioma line (A-172, anaplastic astrocytoma cells). Both peptides were effective, although theα-MSH (1–13) sequence was more potent. Preincubation of the cells withα-MSH (1–13) markedly increased its effectiveness. The anticytokine effect ofα-MSH in glioma cells may be mediated by human melanocortin-1 receptors; mRNA for this receptor subtype was isolated from resting A-l 72 cells. These results, combined with prior evidence of effectiveness ofα-MSH molecules in modulating inflammatory processes and of their low toxicity, suggest that the molecules may be useful in the treatment of CNS disorders that have an inflammatory component.

Original languageEnglish (US)
Pages (from-to)37-41
Number of pages5
JournalNeuroImmunoModulation
Volume4
Issue number1
DOIs
StatePublished - Jan 1 1997

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Keywords

  • CNS disorders
  • Inflammation
  • Neurological disorders
  • Tumor necrosis factor-α
  • α-Melanocyte-stimulating hormone

ASJC Scopus subject areas

  • Immunology
  • Endocrinology
  • Neurology
  • Endocrine and Autonomic Systems

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