ALPHA-MELANOCYTE-STIMULATING HORMONE INHIBITS TUMOR-NECROSIS-FACTOR-ALPHA STIMULATED INTERCELLULAR-ADHESION MOLECULE-1 EXPRESSION IN NORMALCUTANEOUS HUMAN MELANOCYTES AND IN MELANOMA CELL-LINES

alpha-Melanocyte stimulating hormone (alpha-MSH) was found significant ly to reduce tumour necrosis factor-alpha (TNF-alpha) stimulated upreg ulation of intercellular adhesion molecule-1 (ICAM-1) in normal adult cutaneous melanocytes. The maximum inhibitory response to alpha-MSH wa s obtained at around 10(-10) mol/L alpha-MSH when cells were coincubat ed with alpha-MSH and TNF-alpha for 24 h. alpha-MSH had little or no e ffect on basal ICAM-1 expression in melanocytes and the effects of alp ha-MSH could be mimicked with 3-isobutyl-1-methylxanthine (IBMX). Prel iminary data in three human melanoma cell lines also showed alpha-MSH and forskolin to be effective in significantly reducing TNF-alpha stim ulated ICAM-1 expression over 24-h. The extent of the inhibition varie d from cell line to cell line and was greatest in those cells with the highest number of alpha-MSH receptors. These data suggest that alpha- MSH has the ability to oppose the action of the pro-inflammatory cytok ine TNF-alpha on melanocytes and melanoma cells.