alpha-Melanocyte stimulating hormone inhibits tumour necrosis factor-alpha stimulated intercellular adhesion molecule-1 expression in normal cutaneous human melanocytes and in melanoma cell lines.
alpha-Melanocyte stimulating hormone (alpha-MSH) was found significantly to reduce tumour necrosis factor-alpha (TNF-alpha) stimulated upregulation of intercellular adhesion molecule-1 (ICAM-1) in normal adult cutaneous melanocytes. The maximum inhibitory response to alpha-MSH was obtained at around 10(-10) mol/L alpha-MSH when cells were coincubated with alpha-MSH and TNF-alpha for 24 h. alpha-MSH had little or no effect on basal ICAM-1 expression in melanocytes and the effects of alpha-MSH could be mimicked with 3-isobutyl-1-methylxanthine (IBMX). Preliminary data in three human melanoma cell lines also showed alpha-MSH and forskolin to be effective in significantly reducing TNF-alpha stimulated ICAM-1 expression over 24 h. The extent of the inhibition varied 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 cytokine TNF-alpha on melanocytes and melanoma cells.
Hedley
S J
SJ
University Department of Medicine, Clinical Sciences Centre, Northern General Hospital, Sheffield, U.K.
Gawkrodger
D J
DJ
Weetman
A P
AP
Morandini
R
R
Boeynaems
J M
JM
Ghanem
G
G
Neil
S M
SM
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000328:Adult; D018929:Cell Culture Techniques; D005576:Colforsin / Q000494:pharmacology; D017077:Culture Media, Conditioned; D005260:Female; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D008544:Melanocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D008545:Melanoma / Q000276:immunology / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D015854:Up-Regulation; D000521:alpha-MSH / Q000494:pharmacology*
D017077:Culture Media, Conditioned; D009363:Neoplasm Proteins; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D005576:Colforsin; D000521:alpha-MSH; D015056:1-Methyl-3-isobutylxanthine