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      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

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          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.

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          Author and article information

          S. Karger AG
          12 September 1997
          : 4
          : 1
          : 37-41
          Departments of aPhysiology and bAnesthesiology and Pain Management, University of Texas Southwestern Medical Center at Dallas, Tex., USA; cClinica Medica 3, Ospedale Maggiore, Milan, Italy
          97313 Neuroimmunomodulation 1997;4:37–41
          © 1997 S. Karger AG, Basel

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          Pages: 5
          Original Paper


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