Background:Antimicrobial peptides (AMPs) are important effector molecules of innate immunity, protecting epithelial surfaces of multicellular organisms. In h uman skin two classes of AMPs-the β-defensins and the cath...Background:Antimicrobial peptides (AMPs) are important effector molecules of innate immunity, protecting epithelial surfaces of multicellular organisms. In h uman skin two classes of AMPs-the β-defensins and the cathelicidins-are prod uced by keratinocytes primarily under inflammatory conditions. In contrast, derm cidin (DCD), a recently discovered AMP with broad-spectrum activity, is express ed in eccrine sweat glands and transported via sweat to the epidermal surface. O bjectives:To investigate whether DCD expression is induced under inflammatory c onditions in epidermal keratinocytes. Methods:Lesional skin of the inflammatory skin diseases atopic dermatitis, psoriasis and lichen planus was analysed by im munohistochemistry using a polyclonal anti-DCD antiserum. We also examined whet her DCD RNA expression is induced in cultured human keratinocytes, fibroblasts, melanocytes and melanoma cells. Results:Whereas DCD was constitutively expresse d in eccrine sweat glands of all skin biopsies, we found that, independent of th e type of the inflammatory skin lesion, DCD protein expression was not induced i n human epidermal keratinocytes. In contrast, β-defensin 2 was expressed in ep idermal keratinocytes of inflammatory human skin, but not in keratinocytes of he althy human skin. Upon stimulation of the cultured cells with 12-O-tetradecano yl-phorbol -13-acetate, tumour necrosis factor-α, lipopolysaccharide or H2O2,DCD mRNA expression was not detected in primary keratinocytes, fibroblasts and melanocyt es, but was detected in MeWo and SKMEL28 melanoma cells. Conclusions:These resu lts indicate that, unlike human cathelicidins and β-defensinswhichare inducibl e peptides that primarily function in response to injury and inflammation, DCD is exclusively part of the constitutive innate defence of human skin. By m odulating surface colonization, DCD may help to prevent local and systemic invas ion of pathogens.展开更多
文摘Background:Antimicrobial peptides (AMPs) are important effector molecules of innate immunity, protecting epithelial surfaces of multicellular organisms. In h uman skin two classes of AMPs-the β-defensins and the cathelicidins-are prod uced by keratinocytes primarily under inflammatory conditions. In contrast, derm cidin (DCD), a recently discovered AMP with broad-spectrum activity, is express ed in eccrine sweat glands and transported via sweat to the epidermal surface. O bjectives:To investigate whether DCD expression is induced under inflammatory c onditions in epidermal keratinocytes. Methods:Lesional skin of the inflammatory skin diseases atopic dermatitis, psoriasis and lichen planus was analysed by im munohistochemistry using a polyclonal anti-DCD antiserum. We also examined whet her DCD RNA expression is induced in cultured human keratinocytes, fibroblasts, melanocytes and melanoma cells. Results:Whereas DCD was constitutively expresse d in eccrine sweat glands of all skin biopsies, we found that, independent of th e type of the inflammatory skin lesion, DCD protein expression was not induced i n human epidermal keratinocytes. In contrast, β-defensin 2 was expressed in ep idermal keratinocytes of inflammatory human skin, but not in keratinocytes of he althy human skin. Upon stimulation of the cultured cells with 12-O-tetradecano yl-phorbol -13-acetate, tumour necrosis factor-α, lipopolysaccharide or H2O2,DCD mRNA expression was not detected in primary keratinocytes, fibroblasts and melanocyt es, but was detected in MeWo and SKMEL28 melanoma cells. Conclusions:These resu lts indicate that, unlike human cathelicidins and β-defensinswhichare inducibl e peptides that primarily function in response to injury and inflammation, DCD is exclusively part of the constitutive innate defence of human skin. By m odulating surface colonization, DCD may help to prevent local and systemic invas ion of pathogens.
