Melanocyte stimulating hormone peptides inhibit TNF-alpha signaling in human dermal fibroblast cells.
Alpha-melanocyte stimulating hormone (alpha-MSH) has been identified as a potent anti-inflammatory in various tissues including the skin. It has previously been shown in skin cell keratinocytes and melanocytes/melanoma cells that MSH peptides inhibit TNF-alpha stimulated NF-kappaB activity and intercellular adhesion molecule-1 (ICAM-1) upregulation. However, the precise anti-inflammatory role of MSH peptides in dermal fibroblasts is unclear. Some studies report on pro-inflammatory responses, while others on anti-inflammatory responses. The present study confirms MC1R expression in cultured human dermal fibroblasts and reports that the MSH peptides alpha-MSH and KP(-D-)V inhibit TNF-alpha stimulated NF-kappaB activity and ICAM-1 upregulation, consistent with an anti-inflammatory role. However, involvement of IkappaB-alpha regulation by either peptide was not confirmed, supporting a mechanism independent of the NF-kappaB inhibitor. In conclusion, alpha-MSH and KP(-D-)V peptides have an anti-inflammatory action on dermal fibroblast signaling by inhibiting the pro-inflammatory activity of TNF-alpha in vitro.
Hill
R P
RP
University of Sheffield, Department of Engineering Materials, Sir Robert Hadfield Building, Mappin Street, Sheffield, S1 3JD, UK.
MacNeil
S
S
Haycock
J W
JW
D045744:Cell Line, Tumor; D002478:Cells, Cultured; D020405:Dermis / Q000166:cytology*; D005347:Fibroblasts / Q000166:cytology* / Q000276:immunology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D009074:Melanocyte-Stimulating Hormones / Q000494:pharmacology*; D016328:NF-kappa B / Q000378:metabolism; D010455:Peptides / Q000494:pharmacology*; D044102:Receptor, Melanocortin, Type 1 / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000378:metabolism
D016328:NF-kappa B; D010455:Peptides; D044102:Receptor, Melanocortin, Type 1; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D009074:Melanocyte-Stimulating Hormones