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.
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.
Wong
K Y
KY
Department of Physiology, University of Texas Southwestern Medical Center at Dallas 75235-9040, USA.
Rajora
N
N
Boccoli
G
G
Catania
A
A
Lipton
J M
JM
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*
D014409:Tumor Necrosis Factor-alpha; D000521:alpha-MSH