α-Melanocyte stimulating hormone cytoprotective biology in human dermal fibroblast cells

Alpha-melanocyte stimulating hormone (α-MSH) has been identified as a potent anti-inflammatory peptide effective in various tissues including skin. It acts by inhibiting the production and action of several pro-inflammatory stimuli including TNF-α, IL-1β and LPS in a number of cell types. The role of such stimuli in inducing cellular apoptosis is also well described; however the precise role of α-MSH in apoptosis is presently unclear, with studies reporting both anti- and pro-apoptotic activity. The present study demonstrates that cultured human dermal fibroblasts respond to serum depletion and TNF-α, IL-1β and LPS with an increase in membrane permeability, a decrease in viability and an increase in phosphatidylserine externalization (indicative of apoptosis) over 48-96 h. α-MSH (at 10−6 M, but not 10−9 M) was found to inhibit the serum free and pro-inflammatory mediated reduction in membrane permeability and cellular viability and also inhibited increases in apoptosis. In conclusion, data support a cytoprotective and anti-apoptotic role of the α-MSH peptide in human dermal fibroblast cells.