Dermcidin is constitutively produced by eccrine sweat glands and is not induced in epidermal cells under inflammatory skin conditions.
BACKGROUND
Antimicrobial peptides (AMPs) are important effector molecules of innate immunity, protecting epithelial surfaces of multicellular organisms. In human skin two classes of AMPs-the beta-defensins and the cathelicidins-are produced by keratinocytes primarily under inflammatory conditions. In contrast, dermcidin (DCD), a recently discovered AMP with broad-spectrum activity, is expressed in eccrine sweat glands and transported via sweat to the epidermal surface.


OBJECTIVE
To investigate whether DCD expression is induced under inflammatory conditions in epidermal keratinocytes.


METHODS
Lesional skin of the inflammatory skin diseases atopic dermatitis, psoriasis and lichen planus was analysed by immunohistochemistry using a polyclonal anti-DCD antiserum. We also examined whether DCD RNA expression is induced in cultured human keratinocytes, fibroblasts, melanocytes and melanoma cells.


RESULTS
Whereas DCD was constitutively expressed in eccrine sweat glands of all skin biopsies, we found that, independent of the type of the inflammatory skin lesion, DCD protein expression was not induced in human epidermal keratinocytes. In contrast, beta-defensin 2 was expressed in epidermal keratinocytes of inflammatory human skin, but not in keratinocytes of healthy human skin. Upon stimulation of the cultured cells with 12-O-tetradecanoyl-phorbol-13-acetate, tumour necrosis factor-alpha, lipopolysaccharide or H2O2, DCD mRNA expression was not detected in primary keratinocytes, fibroblasts and melanocytes, but was detected in MeWo and SKMEL28 melanoma cells.


CONCLUSIONS
These results indicate that, unlike human cathelicidins and beta-defensins which are inducible peptides that primarily function in response to injury and inflammation, DCD is exclusively part of the constitutive innate defence of human skin. By modulating surface colonization, DCD may help to prevent local and systemic invasion of pathogens.
Rieg
S
S
Department of Dermatology, Eberhard-Karls-University Tübingen, Liebermeisterstr. 25, D-72076 Tübingen, Germany.
Garbe
C
C
Sauer
B
B
Kalbacher
H
H
Schittek
B
B
D000328:Adult; D002478:Cells, Cultured; D003876:Dermatitis, Atopic / Q000378:metabolism; D004439:Eccrine Glands / Q000378:metabolism*; D004817:Epidermis / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism; D008010:Lichen Planus / Q000378:metabolism; D008875:Middle Aged; D010455:Peptides / Q000235:genetics / Q000378:metabolism*; D011565:Psoriasis / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012871:Skin Diseases / Q000378:metabolism*; D023083:beta-Defensins / Q000096:biosynthesis
C106641:DEFB4A protein, human; D010455:Peptides; D023083:beta-Defensins; C442243:dermcidin