title: 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.
abstract: The proinflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) 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-alpha production should promote survival of neural tissue. The neuropeptide alpha-melanocyte stimulating hormone [alpha-MSH (1-13)] inhibits TNF-alpha production 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-alpha production induced by bacterial endotoxin in cells of a human glioma line (A-172, anaplastic astrocytoma cells). Both peptides were effective, although the alpha-MSH (1-13) sequence was more potent. Preincubation of the cells with alpha-MSH (1-13) markedly increased its effectiveness. The anticytokine effect of alpha-MSH in glioma cells may be mediated by human melanocortin-1 receptors; mRNA for this receptor subtype was isolated from resting A-172 cells. These results, combined with prior evidence of effectiveness of alpha-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.
authors.affiliation: Department of Physiology, University of Texas Southwestern Medical Center at Dallas 75235-9040, USA.
authors.forename: K Y
authors.initials: KY
authors.lastname: Wong
authors.forename: N
authors.initials: N
authors.lastname: Rajora
authors.forename: G
authors.initials: G
authors.lastname: Boccoli
authors.forename: A
authors.initials: A
authors.lastname: Catania
authors.forename: J M
authors.initials: JM
authors.lastname: Lipton
mesh_terms: D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D001921:Brain / Q000187:drug effects*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007249:Inflammation / Q000188:drug therapy; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*; D000521:alpha-MSH / Q000494:pharmacology*
chemical_list: D014409:Tumor Necrosis Factor-alpha; D000521:alpha-MSH