Alpha-melanocyte stimulating hormone cytoprotective biology in human dermal fibroblast cells.
Alpha-melanocyte stimulating hormone (alpha-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-alpha, IL-1beta 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 alpha-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-alpha, IL-1beta 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. alpha-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 alpha-MSH peptide in human dermal fibroblast cells.
Hill
Rebecca P
RP
Department of Engineering Materials, Sir Robert Hadfield Building, Mappin Street, Sheffield S13JD, UK.
Wheeler
Paul
P
MacNeil
Sheila
S
Haycock
John W
JW
D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D019610:Cytoprotection; D020405:Dermis / Q000166:cytology*; D005347:Fibroblasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D011135:Polysaccharides, Bacterial / Q000494:pharmacology; D044967:Serum; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D000521:alpha-MSH / Q000494:pharmacology / Q000502:physiology*
D007375:Interleukin-1; D011135:Polysaccharides, Bacterial; D014409:Tumor Necrosis Factor-alpha; D000521:alpha-MSH