Melanocyte stimulating hormone peptides inhibit TNF-α signaling in human dermal fibroblast cells

Alpha-melanocyte stimulating hormone (α-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-α stimulated NF-κB 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 α-MSH and KP-D-V inhibit TNF-α stimulated NF-κB activity and ICAM-1 upregulation, consistent with an anti-inflammatory role. However, involvement of IκB-α regulation by either peptide was not confirmed, supporting a mechanism independent of the NF-κB inhibitor. In conclusion, α-MSH and KP-D-V peptides have an anti-inflammatory action on dermal fibroblast signaling by inhibiting the pro-inflammatory activity of TNF-α in vitro.